Pages

Wednesday, December 24, 2008

OTOF Gene

The official name of OTOF gene is “otoferlin". The OTOF gene provides instructions for making a protein called otoferlin. This protein is present in the brain and the cochlea, which is a snail-shaped structure in the inner ear that helps process sound. Although the exact function of otoferlin is uncertain, it appears to be essential for normal hearing. Researchers believe that otoferlin may play a role in releasing chemical signals (neurotransmitters) from nerve cells that are involved in hearing. This process is dependent on the concentration of calcium within the cell. The otoferlin protein has several regions called C2 domains that bind to calcium and use it to interact with other molecules.

Location:

OTOF Gene is present in human chromosome 2 and its coded from region 26,533,574 to 26,635,069 base pairs with 47 exons, the cytogenetic location 2p23.1.

Disease

Mutations in OTOF gene causes  nonsyndromic deafness     At least 16 mutations in the OTOF gene have been identified in people with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNB9. People with these mutations have a type of hearing loss called auditory neuropathy, which occurs when sound is not transmitted properly from the inner ear to the brain.

    Some mutations in the OTOF gene result in the production of an abnormally small, nonfunctional version of otoferlin or prevent cells from making any of this protein. Other genetic changes probably alter the 3-dimensional structure of otoferlin, which impairs its ability to bind to calcium.

    A particular OTOF mutation is a common cause of nonsyndromic deafness in the Spanish population. This mutation replaces one amino acid building block, glutamine, with a signal that stops protein production prematurely at position 829 in the otoferlin protein (written as Gln829Ter or Q829X). The Q829X mutation causes an abnormally short version of otoferlin to be made, which disrupts the protein's function and leads to hearing loss.

Monday, December 22, 2008

NR4A2 gene

The official name of NR4A2 gene is “nuclear receptor subfamily 4, group A, member 2". The MSH6 gene provides instructions for making a member of steroid-thyroid hormone-retinoid receptor superfamily. that may plays a role as a Trascription factor. This protein found in the brain and the adrenal gland (the hormone-producing gland located on top of each kidney). In the brain, the NR4A2 protein plays a key role in prompting certain nerve cells to specialize (differentiate) and produce a chemical messenger called dopamine. Dopamine transmits messages that help the brain control physical movement and emotional behavior.
NR4A2 prot direct interactions
image coursey: Oliver Brun
Location:

NR4A2 gene is present in human chromosome 2 and its coded from region 156,889,194 to 156,897,445 base pairs with 8 exons, the cytogenetic location 2q22-q23.

Disease

Mutations in this gene have been associated with disorders related to dopaminergic dysfunction, including Parkinson disease, schizophernia, and manic depression. Misregulation of this gene may be associated with rheumatoid arthritis. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Friday, December 12, 2008

MSH6 Gene

The official name of MSH2 gene is “mutS homolog 6 (E. coli)". The MSH6 gene provides instructions for making a protein that plays an essential role in repairing DNA. This protein fixes mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. The MSH6 protein joins with another protein, the MSH2 protein, to form an active protein complex. This active protein complex identifies places on the DNA where mistakes have been made during DNA replication. Another group of proteins, the MLH1-PMS2 protein complex, then takes over to help with the actual repair. The MSH6 gene is a member of a set of genes known as the mismatch repair (MMR) genes.


Location:

MSH2 gene is present in human chromosome 2 and its coded from region 47,863,789 to 47,887,595 base pairs with 16 exons, the cytogenetic location 2p16.

Disease

Mutations in the MSH6 gene have been reported in about 10 percent of families with Lynch syndrome that have an identified gene mutation. All of these mutations cause the production of an abnormally short, nonfunctional MSH6 protein or a partially active version of the protein. When the MSH6 protein is absent or ineffective, the number of mistakes that are left unrepaired during cell division increases substantially. If the cells continue to divide, errors accumulate in DNA; the cells become unable to function properly and may form a tumor in the colon or another part of the body. People with mutations in the MSH6 gene also have an increased risk of developing cancers of the ovary, stomach, small intestine, liver, gallbladder duct, upper urinary tract, brain, and skin.

Friday, December 5, 2008

MSH2 Gene

The official name of MSH2 gene is “mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)". TThe MSH2 gene provides instructions for making a protein that plays an essential role in DNA repair. This protein fixes mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. The MSH2 protein joins with one of two other proteins, the MSH6 protein or the MSH3 protein, to form an active protein complex. This active protein complex identifies places on the DNA where mistakes have been made during DNA replication. Another group of proteins, the MLH1-PMS2 protein complex, then takes over to help with the actual repair. The MSH2 gene is a member of a set of genes known as the mismatch repair (MMR) genes.



Location:

MSH2 gene is present in human chromosome 2 and its coded from region 47,483,766 to 47,563,863 base pairs with 16 exons, the cytogenetic location 2p22-p21.

Disease

Mutations in this gene causes increases the risk of Lynch syndrome, About 40 percent of all cases of Lynch syndrome with an identified gene mutation are associated with mutations in the MSH2 gene. Several hundred MSH2 mutations that predispose people to colorectal cancer and other HNPCC-associated cancers have been found. These mutations may cause the production of an abnormally short or inactivated MSH2 protein that cannot perform its normal function. When the MSH2 protein is absent or ineffective, the number of mistakes that are left unrepaired during cell division increases substantially. If the cells continue to divide, errors accumulate in DNA; the cells become unable to function properly and may form a tumor in the colon or another part of the body. People with mutations in the MSH2 gene have an increased risk of developing several other types of cancer, including cancers of the endometrium (lining of the uterus), ovary, stomach, small intestine, liver, gallbladder duct, upper urinary tract, brain, and skin. Some mutations in the MSH2 gene increase the likelihood of several uncommon skin tumors occurring in addition to colorectal cancer, a combination called Muir-Torre syndrome. These rare skin tumors include sebaceous adenomas and carcinomas, which occur in skin glands (sebaceous glands) that produce an oily substance called sebum. Multiple, rapidly growing skin tumors called keratoacanthomas may also occur, usually on sun-exposed areas.

Wednesday, December 3, 2008

ASPM Gene

Definition:
ASPM is a human gene whose defective forms are associated with autosomal recessive primary microcephaly."ASPM" is an acronym for "Abnormal Spindle-like, Microcephaly-associated", which reflects its being an ortholog to the Drosophila melanogaster "abnormal spindle" (asp) gene.


Chromsome: Chromosome 1


Location :1q31

Size of gene:62291bp (195319997 to195382287 complementary)


No Exons :28

No Introns:27

Description:The ASPM gene is the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts.

Evolutionary significance:
A new allele (version) of ASPM appeared sometime between 14,100 and 500 years ago with a mean estimate of 5,800 years ago. The new allele has a frequency of about 50 percent in populations of the Middle East and Europe, it is less frequent in East Asia, and has low frequencies among Sub-Saharan African populations.

The mean estimated age of the ASPM allele of 5,800 years ago, roughly correlates with the development of written language, spread of agriculture and development of cities. Currently, two alleles of this gene exist: the older (pre-5,800 years ago) and the newer (post-5,800 years ago). About 10% of humans have two copies of the new ASPM allele, while about 50% have two copies of the old allele. The other 40% of humans have one copy of each. Of those with an instance of the new allele, 50% of them are an identical copy suggesting a highly rapid spread from the original mutation. According to a hypothesis called a "selective sweep", the rapid spread of a mutation (such as the new ASPM) through the population indicates that the mutation is somehow advantageous to the individual. As of today, there is no evidence to support the notion that the new ASPM allele increases intelligence, and some researchers dispute whether the spread of the allele even demonstrates selection. They suggest that the current distribution of the alleles could be explained by a founder effect, following an out of Africa dispersal. However, statistical analysis has shown that the older forms of the gene are found more heavily in populations that speak tonal languages like Chinese.

Protein Sequence:Asp (abnormal spindle)-like, microcephaly associated [Homo sapiens].

ACADM Gene

Defintion:
ACADM (acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain) is a gene that provides instructions for making an enzyme called acyl-coenzyme
Chromosome: Chromosome 1

Location: 1p31 (75962870 to 76001771)

Size Of Gene: 38902 bp


Locus :RP4-682C21.1

Number of Exons: 12

Number Of Introns : 11

Description: A dehydrogenase that is important for breaking down (degrading) a certain group of fats called medium-chain fatty acids. These fatty acids are found in foods such as milk and certain oils, and they are also stored in the body's fat tissue. Medium-chain fatty acids are also produced when larger fatty acids are degraded. The acyl-coenzyme A dehydrogenase for medium-chain fatty acids (ACADM) enzyme is essential for converting these particular fatty acids to energy, especially during periods without food (fasting). The ACADM enzyme functions in mitochondria, the energy-producing centers within cells. It is found in the mitochondria of several types of tissues, particularly the liver.


Related conditions
Medium-chain acyl-coenzyme A dehydrogenase deficiency can be caused by mutations in the ACADM gene. More than 30 ACADM gene mutations that cause medium-chain acyl-coenzyme A dehydrogenase deficiency have been identified. Many of these mutations switch an amino acid building block in the ACADM enzyme. The most common amino acid substitution replaces lysine with glutamic acid at position 304 in the enzyme's chain of amino acids (also written as Lys304Glu or K304E). This mutation and other amino acid substitutions alter the enzyme's structure, reducing or abolishing its activity. Other mutations delete or duplicate part of the ACADM gene, which leads to an unstable enzyme that cannot function.

With a shortage (deficiency) of functional ACADM enzyme, medium-chain fatty acids cannot be degraded and processed. As a result, these fats are not converted into energy, which can lead to characteristic symptoms of this disorder, such as lack of energy (lethargy) and low blood sugar. Levels of medium-chain fatty acids or partially degraded fatty acids may build up in tissues and can damage the liver and brain, causing more serious complications.

Protein Coded:NP_000007

"ACADM." Wikipedia, The Free Encyclopedia. 30 Aug 2008, 20:53 UTC. 14 Oct 2008 <http://en.wikipedia.org/w/index.php?title=ACADM&oldid=235248417>.

HADHB Gene

The official name of HADHB gene is hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme. The HADHB gene provides instructions for making part of an enzyme complex called mitochondrial trifunctional protein. This enzyme complex functions in mitochondria, the energy-producing centers within cells. It is found in the mitochondrimitochondrial trifunctional proteina of several tissues, particularly the heart, liver, muscles, and the part of the eye that detects light and color (the retina).Mitochondrial trifunctional protein is required to break down (metabolize) a group of fats called long-chain fatty acids. Long-chain fatty acids are found in foods such as milk and certain oils, and they are also stored in the body's fat tissues. Mitochondrial trifunctional protein is essential for converting long-chain fatty acids to the major source of energy used by the heart and muscles. During periods without food (fasting), this energy source is also important for the liver and other tissues.

Function:
As the name suggests, mitochondrial trifunctional protein performs three functions. It has three enzyme activities that are essential for fatty acid oxidation, which is the multistep process that metabolizes fats and converts them to energy. The beta subunit performs one of the enzyme activities, known as long-chain 3-keto-acyl-coenzyme A thiolase. The alpha subunit carries out the other two enzyme activities.


Location:

HADHA gene is present in human chromosome 2 and its coded from region 26321120 to 26366837 base pairs with 20 exons, the cytogenetic location 2p23.

Disease

Mutations in this gene causes mitochondrial trifunctional protein deficiency.

In mitochondrial trifunctional protein deficiency Researchers have identified at least 20 HADHB gene mutations that reduce all three enzyme activities of mitochondrial trifunctional protein. Most mutations change one of the building blocks (amino acids) used to make the protein's beta subunit. A change in amino acids probably alters the subunit's structure, which disrupts all three activities of the enzyme complex. Some mutations produce abnormally small, unstable beta subunits, which leads to a decreased amount of mitochondrial trifunctional protein. With a loss of mitochondrial trifunctional protein activity, long-chain fatty acids cannot be metabolized and processed. As a result, these fatty acids are not converted to energy, which can lead to the characteristic features of this disorder, such as lethargy and low blood sugar. Long-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver, heart, and muscles, causing more serious complications.

Carnitine palmitoyltransferase II

Definition
Carnitine palmitoyltransferase II, also known as CPT2, is a human gene also known has CPTASE

Chromosome: Chromosome 1

Position:1p32

Size Of Gene:  17767 bp (53434689..53452455)

No Exons 5

Description
Carnitine palmitoyltransferase II precursor (CPT2) is a nuclear protein which is transported to the mitochondrial inner membrane. CPT2 together with carnitine palmitoyltransferase I oxidizes long-chain fatty acids in the mitochondria. Defects in this gene are associated with mitochondrial long-chain fatty-acid (LCFA) oxidation disorders and carnitine palmitoyltransferase II deficiency.[



Disease:
Carnitine palmitoyltransferase II deficiency is a condition that prevents the body from converting certain fats called long-chain fatty acids into energy, particularly during periods without food (fasting),three main types of carnitine palmitoyltransferase II deficiency are: a lethal neonatal form; a severe infantile form that affects the liver, heart, and muscles (hepatocardiomuscular form); and a less severe form that affects only the muscles (myopathic form). Infants with the lethal neonatal form of this disorder usually experience respiratory failure, liver failure, seizures, and an irregular heart beat (arrythmia) leading to cardiac arrest. In many cases, the brain and kidneys are also abnormal. Usually, affected infants do not survive their first year.

COL11A1 Gene

Definition:

Collagen, type XI, alpha 1, also known as COL11A1, is a human gene.

Chromosome:Chromosome 1

Location: 1p21

Size of gene: 232030 bp (5001..237030)

No Exons:67

Description:

This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Mutations in this gene are associated with type II Stickler syndrome and with Marshall syndrome. A single-nucleotide polymorphism in this gene is also associated with susceptibility to lumbar disc herniation. Three transcript variants encoding different isoforms have been identified for this gene.


Disease:Stickler syndrome - caused by mutations in the COL11A1 gene


Mutations in the COL11A1 gene have been identified in some people with Stickler syndrome. Some mutations change one of the protein building blocks (amino acids) used to make the pro-alpha1(XI) chain. Other mutations cause segments of DNA to be skipped when the protein is being made, resulting in an abnormally short pro-alpha1(XI) chain. These alterations of type XI collagen impair its function, which can lead hearing loss, a tearing of the lining of the eye (retinal detachment), and abnormalities of the bones and joints.

Mutations in the COL11A1 gene are also responsible for some cases of Marshall syndrome, a disorder that is very similar to Stickler syndrome. In most mutations that cause this syndrome, a segment of DNA is skipped when the protein is made, resulting in an abnormally small pro-alpha1(XI) chain. This shortened protein hinders the formation of mature type XI collagen, which results in the features of Marshall syndrome. Whether Marshall syndrome represents a variant form of Stickler syndrome or a separate disorder is controversial.



Protein:

1464 amino acids. The a1 (I) chains of the type I collagen are synthesised as procollagen molecules containing amino and carboxy-terminal propeptides, wich are removed by site-specific endopeptidase. The central triple helical domain is formed by 338 repeats of a Gly-X-Y triplet where X and Y are often a proline.


Type I collagen is the most abundant protein in vertebrates and a constituent of the extra cellular matrix in connective tissue of bone, skin, tendon, ligament and dentine. It is mostly produced and secreted by fibroblasts and osteoblasts.

Tuesday, December 2, 2008

HADHA Gene

The official name of HADHA gene is hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha subunit. The HADHA gene provides instructions for making part of an enzyme complex called mitochondrial trifunctional protein. This enzyme complex functions in mitochondria, the energy-producing centers within cells. It is found in the mitochondria of several tissues, particularly the heart, liver, muscles, and the part of the eye that detects light and color (the retina).

Function:
Mitochondrial trifunctional protein is required to break down (metabolize) a group of fats called long-chain fatty acids. Long-chain fatty acids are found in foods such as milk and certain oils, and they are also stored in the body's fat tissues. Mitochondrial trifunctional protein is essential for converting long-chain fatty acids to the major source of energy used by the heart and muscles. During periods without food (fasting), this energy source is also important for the liver and other tissues.Mitochondrial trifunctional protein is made of eight subunits. Four subunits called alpha are produced by the HADHA gene, and four subunits called beta are produced by the HADHB gene. As the name suggests, mitochondrial trifunctional protein performs three functions. It has three enzyme activities that are essential for fatty acid oxidation, which is the multistep process that metabolizes fats and converts them to energy. The alpha subunit performs two of the enzyme activities, known as long-chain 3-hydroxyacyl-coenzyme A dehydrogenase and long-chain 2-enoyl-coenzyme A hydratase. The beta subunit carries out the third enzyme activity.

Location:

HADHA gene is present in human chromosome 2 and its coded from region 26267008 to 26321098 base pairs with 20 exons, the cytogenetic location 2p23.

Disease

Mutations in this gene causes long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency(LCAD defiency) and Mitochondrial trifunctional protein deficiency

In LCAD defiency Researchers have identified several HADHA gene mutations that decrease the long-chain 3-hydroxyacyl-coenzyme A dehydrogenase enzyme activity of the mitochondrial trifunctional protein. (The protein's other enzyme activities remain normal or near normal.) Many of the HADHA mutations change one of the building blocks (amino acids) used to make the protein's alpha subunit. The most common mutation replaces the amino acid glutamic acid with the amino acid glutamine at position 474 in the alpha subunit. This mutation is written as Glu474Gln or E474Q. The Glu474Gln mutation and other amino acid replacements probably alter the structure of the alpha subunit, preventing it from functioning normally. Other types of HADHA mutations produce an abnormally small, unstable alpha subunit, which is unable to function. With a shortage (deficiency) of functional alpha subunits, long-chain fatty acids cannot be metabolized and processed. As a result, these fatty acids are not converted to energy, which can lead to the characteristic features of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, such as lack of energy (lethargy) and low blood sugar. Long-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver, heart, and retina, causing more serious complications.

In mitochondrial trifunctional protein deficiency Researchers have identified several HADHA gene mutations that reduce all three enzyme activities of the mitochondrial trifunctional protein. Some mutations produce abnormally small, unstable alpha subunits, which leads to a decreased level of mitochondrial trifunctional protein. Other mutations replace one amino acid with another amino acid in the alpha subunit, which probably alters the subunit's structure and disrupts all three functions of the enzyme complex. With a loss of mitochondrial trifunctional protein activity, long-chain fatty acids cannot be metabolized and processed. As a result, these fatty acids are not converted to energy, which can lead to the characteristic features of this disorder, such as lethargy and low blood sugar. Long-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver, heart, and muscles, causing more serious complications.

COL5A2 Gene


The official name of COL5A2 gene is collagen, type V, alpha 2. The COL5A2 gene provides instructions for making a component of collagen. Collagens form a family of proteins that strengthen and support many tissues in the body, including skin, ligaments, bones, tendons, muscles, and the space between cells and tissues called the extracellular matrix.

Function:
The COL5A2 gene produces a component of type V collagen, called the pro-alpha2(V) chain. One pro-alpha2(V) chain combines with two pro-alpha1(V) chains (produced by the COL5A1 gene) to form type V procollagen. These triple-stranded, rope-like procollagen molecules must be processed by enzymes outside the cell. Once these molecules are processed, they arrange themselves into long, thin fibrils that cross-link to one another in the spaces around cells. The cross-links result in the formation of very strong, mature type V collagen fibers. Type V collagen also plays a role in assembling other types of collagen into fibrils within many connective tissues.


Location:
COL5A2 gene is present in human chromosome 2 and its coded from region 189604886 to 189752850 base pairs with 54 exons, the cytogenetic location 2q14-q32.


Disease
Mutations in this gene causes Ehlers-Danlos syndrome,Mutations in the COL5A2 gene have been identified in a small number of patients with classic Ehlers-Danlos syndrome. These mutations change the structure and function of the pro-alpha2(V) chain. As a result, type V collagen fibrils in the skin that are assembled with the altered protein are large and irregular. Researchers believe that these changes in collagen structure cause the signs and symptoms of classic Ehlers-Danlos syndrome.


Ehlers-Danlos syndrome

Monday, December 1, 2008

COL4A3 Gene

The official name of COL4A3 gene is collagen, type IV, alpha 3 (Goodpasture antigen). COL4A3 gene provides instructions for making one component of type IV collagen. which is a flexible protein that forms complex networks. Specifically, this gene makes the alpha3(IV) chain of type IV collagen. This chain combines with two other types of alpha (IV) chains (the alpha4 and alpha5 chains) to make a complete collagen molecule. Type IV collagen networks make up a large portion of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. This specific type IV collagen network plays an especially important role in the basement membranes of the kidney, inner ear, and eye.

Function:
Type IV collagen, the major structural component of basement membranes, is a multimeric protein composed of 3 alpha subunits. These subunits are encoded by 6 different genes, alpha 1 through alpha 6, each of which can form a triple helix structure with 2 other subunits to form type IV collagen. This gene encodes alpha 3.In the Goodpasture syndrome, autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are localized largely to the non-collagenous C-terminal domain of the protein.
Collagen

Location:

COL4A3 gene is present in human chromosome 2 and its coded from region 227,737,524 to base pair 227,887,750 with 52 exons, the cytogenetic location 2q36-q37

Disease

Mutations in this gene causes Alport syndrome,The autosomal recessive form of Alport syndrome results when two copies of the COL4A3 gene in each cell are mutated. Most of the mutations identified in this gene cause a change in the sequence of amino acids (the building blocks of proteins) in a region of the alpha3(IV) collagen chain that is critical for combining with other type IV collagen chains. Other mutations severely decrease or prevent the production of any alpha3(IV) chains in the basement membranes of the kidney, inner ear and eye. In the kidney, other types of collagen accumulate in the basement membranes, eventually leading to scarring of the kidneys and kidney failure. Mutations in this gene can also lead to abnormal function in the inner ear, resulting in hearing loss.

COL3A1 Gene

The official name of COL3A1 gene is collagen, type III, alpha 1. COL3A1 gene provides instructions for making a component of collagen. Collagens form a family of proteins that strengthen and support many tissues in the body. Type III collagen is found in tissues such as the skin, lungs, intestinal walls, and the walls of blood vessels. The COL3A1 gene produces the components of type III collagen, called pro-alpha1(III) chains.Three copies of this chain combine to make a molecule of type III procollagen. These triple-stranded, rope-like procollagen molecules must be processed by enzymes outside the cell to remove extra protein segments from their ends. Once these molecules are processed, the collagen molecules arrange themselves into long, thin fibrils. Within these fibrils, the individual collagen molecules are cross-linked to one another. These cross-links result in the formation of very strong mature type III collagen fibrils, which are found in the spaces around cells.

Function
Collagen protein strengthens and supports tissues

Location:
COL3A1 gene is present in human chromosome 2 and its coded from region189,547,343 to 189,585,716 with 51 exons, the cytogenetic location 2q31

Disease

Mutations in this gene causes Ehlers-Danlos syndrome,Researchers have identified more than 320 mutations mutations that cause the vascular type of Ehlers-Danlos syndrome have been identified in the COL3A1 gene. Only a few of these mutations have been seen in more than one family. The mutations alter the structure and production of type III procollagen molecules. As a result, a large percentage of type III collagen molecules are assembled incorrectly, or the amount of type III collagen is greatly reduced. Researchers believe that these changes affect tissues that are normally rich in this type of collagen, such as the skin, blood vessels, and internal organs. Lack of sufficient type III collagen causes the signs and symptoms of vascular Ehlers-Danlos syndrome.

Wednesday, November 26, 2008

BMPR2 gene

The official name of BMPR2 gene is bone morphogenetic protein receptor, type II (serine/threonine kinase).The BMPR2 gene provides instructions for making a protein called bone morphogenetic protein receptor. Bone morphogenetic protein receptor, type II spans the cell membrane, so that one end of the protein is on the outer surface of the cell and the other end remains inside the cell. This arrangement allows the protein to receive and transmit signals that help the cell respond to its environment by growing and dividing (cell proliferation) or by undergoing controlled cell death (apoptosis). This balance of cell proliferation and cell death regulates the number of cells in tissues.

Function:
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Binds to BMP-7, BMP-2 and, less efficiently, BMP-4. Binding is weak but enhanced by the presence of type I receptors for BMPs



Location:
BMPR gene is present in human chromosome 2 and its coded from region 202,949,916 to 203,140,719 with 13 exons, the cytogenetic location 2q33-q34

Disease
Mutations in this gene have been associated with primary pulmonary hypertension, both familial and fenfluramine-associated, and with pulmonary venoocclusive disease.Researchers have identified more than 140 BMPR2 mutations that cause pulmonary arterial hypertension. About half of these mutations disrupt the assembly of bone morphogenetic protein receptor, type II, reducing the amount of this protein in cells. Other mutations prevent bone morphogenetic protein receptor, type II from reaching the cell surface, or alter its structure so it cannot receive or transmit signals.









It remains unclear how BMPR2 mutations cause pulmonary arterial hypertension. Researchers suggest that a mutation in this gene promotes cell proliferation or prevents cell death, resulting in an overgrowth of cells in the smallest arteries throughout the lungs. As a result, these arteries narrow in diameter, which increases the resistance to blood flow through the lungs. To overcome the increased resistance, pressure increases in the pulmonary artery and in the heart chamber that pumps blood into the pulmonary artery (the right ventricle). Signs and symptoms of pulmonary arterial hypertension occur when increased pressure cannot fully overcome the elevated resistance and blood flow to the body is insufficient.

Tuesday, November 25, 2008

ALS2 Gene

The official name of ALS2 gene is amyotrophic lateral sclerosis 2 (juvenile)..The ALS2 gene provides instructions for making a protein called alsin. Alsin is produced in a wide range of tissues, with highest amounts in the brain. It is particularly abundant in motor neurons, the specialized nerve cells in the brain and spinal cord that control the movement of muscles.

Alsin's function in cells is unclear. It may play a role in regulating cell membrane organization and the movement of molecules inside cells. Research findings also suggest that alsin may play a role in the development of axons and dendrites, which are specialized outgrowths from nerve cells that are essential for the transmission of nerve impulses.


Location:
ALS2 gene is present in human chromosome 2 and ts coded from region 202,273,521 to 202,353,982 with 34 exons, the cytogenetic location 2q33.2

Disease
Mutation in the ALS2 Gene causes Amyotrophic lateral Sclerosis(ALS),infantile-onset ascending hereditary spastic paralysis ,juvenile primary lateral sclerosis.In all three disease mutations delete a single DNA building block (nucleotide), which alters the instructions for producing alsin. As a result, alsin is unstable and decays rapidly.

ALMS1 Gene

The official name of ALMS1 gene is Alstrom syndrome 1.The ALMS1 gene provides instructions for making a protein whose function is unknown. Researchers believe that the protein may play a role in hearing, vision, regulation of body weight, and functions of the heart, kidney, lungs, and liver. It may also affect how the pancreas regulates insulin, a hormone that helps control blood sugar levels.

The ALMS1 protein is present in most of the body's tissues, usually at low levels. Within cells, this protein is located in structures called centrosomes. Centrosomes play a role in cell division and the assembly of microtubules, which are proteins that transport materials in cells and help the cell maintain its shape. The ALMS1 protein is also found at the base of cilia, which are finger-like projections that stick out from the surface of cells. Almost all cells have cilia at some stage of their life cycle. Cilia are involved in cell movement and many different chemical signaling pathways. Based on its location within cells, researchers suggest that the ALMS1 protein might be involved in the organization of microtubules, the transport of various materials, and the normal function of cilia.


Location:
ALMS1 gene is present in human chromosome 2 and ts coded from region 73,466,393 to 73,690,553 with 23 exons, the cytogenetic location 2p13

Disease
Mutation in the ALMS1 Gene causes Alström syndrome. Most of these mutations lead to the production of an abnormally small version of the ALMS1 protein that does not function properly. Researchers propose that a lack of normal ALMS1 function in the brain could lead to overeating. A loss of this protein in the pancreas may cause insulin resistance, a condition in which the body cannot use insulin properly. The combined effects of overeating and insulin resistance impair the body's ability to handle excess sugar, leading to diabetes and obesity (two common features of Alström syndrome). It is unclear how ALMS1 mutations cause the other signs and symptoms of Alström syndrome. Researchers suspect that this condition is associated with malfunctioning cilia in many of the body's tissues and organs.

AGXT gene

The official name of AGXT gene is alanine-glyoxylate aminotransferase.The AGXT gene provides instructions for making a liver enzyme called alanine-glyoxylate aminotransferase gene is expressed only in the liver and the encoded protein is localized mostly in the peroxisomes.This protein is important for several cellular activities such as ridding the cell of toxic substances and helping to break down certain fats. Peroxisomes contain several enzymes that are imported from the internal fluid of the cell (cytosol). Enzymes that are transferred into peroxisomes have a special arrangement of building blocks (amino acids) at one end of the enzyme that serves as a shipping address. In the peroxisome, alanine-glyoxylate aminotransferase converts a compound called glyoxylate to the amino acid glycine, which is later used for making enzymes and other proteins.

Peroxisome Proliferator-Activated Receptors


Location:
AGXT gene is present in human chromosome 2 and ts coded from region241456835 to 241467210 with 11 exons, the cytogenetic location 2q36-q37.

Disease
Mutation in the AGXT Gene causes type 1 primary hyperoxaluria. In some type 1 primary hyperoxaluria cases, alanine-glyoxylate aminotransferase enzyme activity is partially or entirely absent because of a mutation. As a result of this enzyme shortage, glyoxylate accumulates and is converted to a compound called oxalate instead of glycine. Oxalate, in turn, combines with calcium to form calcium oxalate, which the body cannot readily eliminate. Deposits of calcium oxalate can lead to kidney stones, kidney damage or failure, and injury to other organs, which are characteristic features of primary hyperoxaluria.

In other people with type 1 primary hyperoxaluria, the alanine-glyoxylate aminotransferase enzyme is misplaced within the cell. Misplacement occurs when certain mutations combine with a natural variation (polymorphism) in the gene. In most cases, a mutation replaces the amino acid glycine with the amino acid arginine at position 170 in the enzyme (written as Gly170Arg or G170R). This mutation occurs with a polymorphism that replaces the amino acid proline with the amino acid leucine at position 11 (written as Pro11Leu or P11L). The combined effect of the mutation and the polymorphism alters the structure of alanine-glyoxylate aminotransferase and changes the cellular shipping address of the enzyme. Instead of locating in peroxisomes, the enzyme is misdelivered to mitochondria, the energy-producing centers of cells. Even though the enzyme retains some of its activity, it cannot make contact with glyoxylate, which is located in peroxisomes. As a result, glyoxylate accumulates, leading to the signs and symptoms of primary hyperoxaluria.

Thursday, November 20, 2008

ABCG8 Gene

The official name of ABCG8 is ATP-binding cassette, sub-family G (WHITE), member 8 (sterolin 2).The ABCG8 gene provides instructions for making a Sterolin-2 protein.Sterolin-1 and –2 are two ‘half’ adenosine triphosphate binding (ATP) cassette (ABC) transporters which found to be indispensable for the regulation of sterol absorption and excretion.The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. The protein encoded by this gene functions to exclude non-cholesterol sterol entry at the intestinal level, promote excretion of cholesterol and sterols into bile, and to facilitate transport of sterols back into the intestinal lumen. It is expressed in a tissue-specific manner in the liver, intestine, and gallbladder. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG5.
Location:
ABCG5 gene is present in human chromosome 2 and ts coded from region 43919607 to 43959109 complement with 13 exons, the cytogenetic location 2p21.

Disease
Mutations in both alleles of either ABCG5 or ABCG8 in the human results in sitosterolemia. Sitosterolemia (also known as phytosterolemia) is a rare autosomal recessively inherited lipid metabolic disorder characterized by the presence of tendon xanthomas, premature coronary artery disease and atherosclerotic disease, hemolytic episodes, arthralgias and arthritis. The hallmark of sitosterolemia is diagnostically elevated levels of plant sterols in the plasma.

Wednesday, November 19, 2008

ABCG5 Gene

The official name of ABCG5 is ATP-binding cassette, sub-family G (WHITE), member 5.The ABCG5 gene provides instructions for making a sterolin1 protein OF ABC group proteins. Sterolin-1 and –2 are two ‘half’ adenosine triphosphate binding (ATP) cassette (ABC) transporters which found to be indispensable for the regulation of sterol absorption and excretion.

Location:
ABCG5 gene is present in human chromosome 2 and ts coded from region 43893115 to 43919462 complement with 13 exons, the cytogenetic location 2p21.

Disease
Mutations in both alleles of either ABCG5 or ABCG8 in the human results in sitosterolemia. Sitosterolemia (also known as phytosterolemia) is a rare autosomal recessively inherited lipid metabolic disorder characterized by the presence of tendon xanthomas, premature coronary artery disease and atherosclerotic disease, hemolytic episodes, arthralgias and arthritis. The hallmark of sitosterolemia is diagnostically elevated levels of plant sterols in the plasma.

ABCA12 Gene

The official name of ABCA12 is ATP-binding cassette, sub-family A (ABC1), member 12.The USH2A gene provides instructions for making a protein called ATP-binding cassette (ABC) transporter. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants.

Location:
USH2A gene is present in human chromosome 2 and ts coded from region 215504511 to 215711396 complement with 53 exons, the cytogenetic location 2q34.

Disease
Mutations iin the ABCA12 gene have been identified in people with harlequin ichthyosis. Harlequin ichthyosis is a severe genetic disorder that mainly affects the skin. Infants with this condition are born with very hard, thick skin covering most of their bodies. The skin forms large, diamond-shaped plates that are separated by deep cracks (fissures). These skin abnormalities affect the shape of the eyelids, nose, mouth, and ears, and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties and respiratory failure.ABCA12 gene mutations probably lead to an absence of ABCA12 protein or the production of an extremely small version of the protein that cannot transport lipids properly. A lack of lipid transport causes numerous problems with the development of the epidermis before and after birth. Specifically, it prevents the skin from forming an effective barrier against fluid loss (dehydration) and infections, and leads to the formation of hard, thick scales characteristic of harlequin ichthyosis.


The below Video is in very disturbing.I added this video only to show how cruel this disorder is.

Monday, November 17, 2008

USH2A gene

The official name of USH2A gene is Usher syndrome 2A (autosomal recessive, mild)..The USH2A gene provides instructions for making anan enzyme called usherin. Usherin is an important component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Usherin is found in the inner ear and the part of the eye that detects light and color (the retina). Although the function of usherin has not been well established, studies suggest that this protein is part of a larger protein complex that plays an important role in inner ear and retinal development. In these locations, the protein complex may also be involved in the function of synapses, which are junctions between nerve cells where cell-to-cell communication occurs.

Location
:
USH2A gene is present in human chromosome 1 and ts coded from region 213,862,858 to 214,663,360 complement with 71 exons, the cytogenetic location 1q41.


Disease
Mutations in USH2A gene causes a form of  Usher syndrome type IIA,Usher syndrome is a condition characterized by hearing loss or deafness and progressive vision loss. The loss of vision is caused by an eye disease called retinitis pigmentosa (RP), which affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate.Mutations change single protein building blocks (amino acids) in the usherin protein. In some cases, these mutations lead to the production of an abnormally short version of the protein or prevent the cell from making any functional usherin. Other mutations insert or delete small amounts of DNA in the USH2A gene, which probably impairs the normal function of usherin. Researchers have not determined how a missing or altered usherin protein leads to the signs and symptoms of Usher syndrome.The most common mutation in the USH2A gene is found in about 25 percent of people with Usher syndrome type IIA, particularly those from Europe, the United States, South Africa, and China. This mutation deletes a specific DNA building block, a guanine (G) nucleotide, at position 2299 in the USH2A gene (written as 2299delG). Individuals with this change, or with similar mutations in the USH2A gene, develop moderate to severe hearing loss and retinitis pigmentosa, a disorder that results in loss of vision.

UROD Gene

The official name of UROD gene is uroporphyrinogen decarboxylase.The UROD gene provides instructions for making anan enzyme called uroporphyrinogen decarboxylase. Uroporphyrinogen III decarboxylase (UroD) is a homodimeric enzyme which catalyzes the fifth step in heme biosynthesis: the elimination of carboxyl groups from the four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III.Three additional enzymes modify this product before it becomes heme. The heme molecule is then incorporated into hemoglobin and packaged into red blood cells, or it is used in the liver for the production of certain liver enzymes.

Location:
UROD gene is present in human chromosome 1 and ts coded from region 45250417 to 45253928 with 10 exons, the cytogenetic location 1p34.


Disease
Mutations in UROD gene causes a form of porphyria called porphyria cutanea tarda and hepatoerythropoietic porphyria,In porphyria cutanea tarda the mutations occur in one of the two copies of the UROD gene in each cell, which usually reduces the activity of uroporphyrinogen decarboxylase by 50 percent throughout the body.As a result, byproducts of heme production called porphyrins build up in the body, particularly in the liver. This buildup, in combination with nongenetic factors (such as alcohol, smoking, certain hormones, excess iron, and viral infections), causes this type of porphyria.

In hepatoerythropoietic porphyria Most of the mutations are unique in this type of porphyria and have not been found in porphyria cutanea tarda. Mutations that cause hepatoerythropoietic porphyria occur in both copies of the UROD gene in each cell, which reduces the activity of uroporphyrinogen decarboxylase to less than 10 percent of normal. Extremely low levels of this enzyme prevent sufficient amounts of heme from being produced. As a result, byproducts of heme production called porphyrins build up in the body, causing this type of porphyria.

Saturday, November 8, 2008

TSHB Gene

The official name of TSHB gene is thyroid stimulating hormone, beta.The TSHB gene provides instructions for making a protein subunit of a hormone called thyroid stimulating hormone (TSH). Thyroid stimulating hormone consists of two subunits called alpha and beta. The TSHB gene provides instructions for making the beta (B) subunit of thyroid stimulating hormone. The alpha and beta subunits are bound together to produce the active form of the hormone. A particular segment of the beta subunit, known as the buckle or seatbelt, wraps around the alpha subunit to form the functional hormone.
Thyroid stimulating hormone is made in the pituitary gland, a gland at the base of the brain. This hormone plays an important role in the growth and function of the thyroid gland, a butterfly-shaped tissue in the lower neck. It also stimulates the production of thyroid hormones, which play a critical role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). The pituitary gland monitors levels of thyroid hormones. When thyroid hormone levels are too low, the pituitary gland releases thyroid stimulating hormone into the bloodstream. Thyroid stimulating hormone, in turn, signals increased thyroid gland growth and production of thyroid hormones.



Location:
TSHB gene is present in human chromosome 1 and ts coded from region 115373938 to 115378464, the cytogenetic location 1p13


Disease

Researchers have identified several TSHB mutations that alter the size or shape of the thyroid stimulating hormone beta subunit. Many of these mutations affect the beta subunit's seatbelt region, which holds the alpha subunit in place and stabilizes the hormone's structure. Some mutations severely shorten the beta subunit, eliminating the seatbelt region partially or entirely. Other mutations change the chemical building blocks (amino acids) used to make the beta subunit. As a result, the seatbelt region cannot buckle around the alpha subunit. TSHB mutations prevent the production of functional thyroid stimulating hormone or its release (secretion) from the pituitary gland. As a result, thyroid hormone production is not stimulated, leading to low hormone levels that are characteristic of congenital hypothyroidism. Additionally, the thyroid gland is reduced in size (hypoplastic) because its growth is not stimulated.

Thursday, November 6, 2008

SDHB Gene

The official name of SDHB gene is succinate dehydrogenase complex, subunit B, iron sulfur (Ip),The SDHB  gene provides instructions for making a protein called succinate dehydrogenase(SDH). The succinate dehydrogenase (SDH) protein complex catalyzes the oxidation of succinate (succinate + ubiquinone => fumarate + ubiquinol). The SDHB subunit is connected to the SDHA subunit on the hydrophilic, catalytic end of the SDH complex. It is also connected to the SDHC/SDHD subunits on the hydrophobic end of the complex anchored in the mitochondrial membrane. The subunit is an iron-sulfur protein with three iron-sulfur clusters. It weighs 30 kDa.The SDH complex is located on the inner membrane of the mitochondria and participates in both the Citric Acid Cycle and Respiratory chain.

SDHB acts as an intermediate in the basic SDH enzyme action:

   1. SDHA converts succinate to fumarate as part of the Citric Acid Cycle. This reaction also converts FAD to FADH2.
   2. Electrons from the FADH2 are transferred to the SDHB subunit iron clusters [2Fe-2S],[4Fe-4S],[3Fe-4S].
   3. Finally the electrons are transferred to the Ubiquinone (Q) pool via the SDHC/SDHD subunits.This function is part of the Respiratory chain.



Sporadic and familial mutations in this gene result in paragangliomas (glomus tumors)and pheochromocytoma, and support a link between mitochondrial dysfunction and tumorigenesis.
Mutations causing disease have been seen in exons 1 through 7, but not 8. As with the SDHC and SDHD genes, SDHB is a tumor suppressor gene. Note the SDHA gene is not a tumor suppressor gene.

Tumor formation generally follows the Knudson "two hit" hypothesis. The first copy of the gene is mutated in all cells, however the second copy functions normally. When the second copy mutates in a certain cell due to a random event, Loss of Heterozygosity (LOH) occurs and the SDHB protein is no longer produced. Tumor formation then becomes possible.

Given the fundamental nature of the SDH protein in all cellular function, it is not currently understood why only paraganglionic cells are affected. However, the sensitivity of these cells to oxygen levels may play a role.

Tuesday, November 4, 2008

PSEN2 gene

The official name of PSEN2 gene is presenilin 2 (Alzheimer disease 4),The PSEN2 gene provides instructions for making a protein called presenilin 2. Presenilin 2 helps process certain proteins that are important for transmitting biochemical signals from the cell membrane into the nucleus of the cell. In the nucleus, these signals turn on (activate) particular genes that are important for cell growth and maturation. Presenilin 2 is also involved in processing amyloid precursor protein, which is found in the brain and other tissues. Research suggests that presenilin 2 works as part of an enzyme complex that cuts amyloid precursor protein into smaller segments (peptides). One of these peptides is called soluble amyloid precursor protein (sAPP) and another is called amyloid beta peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of nerve cells in both embryonic and adult brain tissue. Other functions of sAPP and amyloid beta peptide are under investigation.

Location:
PSEN gene is present in human chromosome 1 and ts coded from region 225124896 to 225150427, the cytogenetic location 1q31-q42

Disorder:
Mutations in this gene causes Alzheimer's disease 4
Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1 or PSEN2) or the amyloid precursor protein (APP).Researcher have found approxiametly 11 mutaions in PSEN gene have been shown to cause type 4 Alzheimer disease.Two of the most common PSEN2 mutations that cause type 4 Alzheimer disease change one of the building blocks (amino acids) used to make presenilin 2. One mutation replaces the amino acid asparagine with the amino acid isoleucine at position 141 (written as Asn141Ile or N141I). The other mutation changes the amino acid methionine to the amino acid valine at position 239 (written as Met239Val or M239V). These mutations appear to affect the processing of amyloid precursor protein.These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor such that, they either directly regulate gamma-secretase activity, or themselves act are protease enzymes. Two alternatively spliced transcript variants encoding different isoforms of PSEN2 have been identified.

Friday, October 31, 2008

PPOX Gene

 PPOX Gene provides informations to produce an enzyme called protoporphyrinogen oxidase ,This enzyme is responsible for the seventh step in the production of heme, the iron-containing part of hemoglobin.Hemoglobin is the oxygen-carrying protein in red blood cells. Each step in heme production is controlled by a different enzyme, each of which is produced from a single gene. Protoporphyrinogen oxidase removes hydrogen atoms from protoporphyrinogen IX (the product of the sixth step in the production of heme) to form protoporphyrin IX. One additional enzyme modifies protoporphyrin IX before it becomes heme. The heme molecule is incorporated into hemoglobin and packaged into red blood cells, or it is used in the liver for the production of certain liver enzymes.

Location

PPOX gene is present in human chromosome1 and its coded from the region 159402818 to 159407634,the cytogenetic location 1q22, the gene size is 4817 bp with 13 exonic regions

Disorder:

Mutations in this gene causes a  porphyria disorder

More than 100 mutations that cause a form of porphyria called variegate porphyria have been identified in the PPOX gene. A particular mutation that changes one of the building blocks (amino acids) used to make protoporphyrinogen oxidase is found in about 95 percent of South African families with variegate porphyria. Specifically, this genetic change substitutes the amino acid tryptophan for the amino acid arginine at position 59 (written as Arg59Trp or R59W). Mutations in the PPOX gene reduce the activity of protoporphyrinogen oxidase, allowing byproducts of heme production to build up in the body. This buildup, in combination with nongenetic factors (such as certain drugs, alcohol, and dieting), causes this type of porphyria.

Thursday, October 30, 2008

PLOD1 Gene

The official name PLOD1 gene procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1,the Gene provides informations to produce an enzyme called lysyl hydroxylase 1,Lysyl hydroxylase is a membrane -homodimeric protein localized to the citernae of the endoplasmic reticulum.This enzyme modifies a particular amino acid called lysine, which is one of the building blocks used to make proteins. Specifically, lysyl hydroxylase 1 adds a single oxygen atom to a hydrogen atom to create a charged molecule called a hydroxyl group,The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks,Cross-links between these molecules allow collagen to form networks of strong, slender fibrils, which are an important part of the normal structure of connective tissue.


Location
PLOD1 gene is present in human chromosome1 and it is coded from the region from 1917333 to 11958181,the cytogenetic location 1p36.3-p36.2,tHe gene size is 40849 bp with 19 exons

Disease
Mutaions in this gene causes a Ehlers-Danlos syndrome.Researchers have identified more than 20 mutations in PLOD1 gene in affected persons,These mutations cause a form of Ehlers-Danlos syndrome called the kyphoscoliosis type,The most common mutation duplicates a large portion of the gene, resulting in the production of a nonfunctional version of the lysyl hydroxylase 1 enzyme. Several other mutations introduce premature stop signals that prevent the gene from making any functional enzyme. A loss of lysyl hydroxylase 1 activity impairs cross-linking between collagen molecules. This disruption in the network of collagen fibrils weakens connective tissues, causing the signs and symptoms of Ehlers-Danlos syndrome.

Tuesday, October 28, 2008

PINK1 gene

The official name of this gene is PTEN induced putative kinase 1,Gene provides informations to produce serine/threonine protein kinase that localizes to mitochondria,it is function of PTEN induced putative kinase 1 is not fully understood. It appears to help protect mitochondria from malfunctioning during periods of cellular stress, such as unusually high energy demands,Researchers believe that two specialized regions of PTEN induced putative kinase 1 are essential for the protein to function properly. One region, called the mitochondrial-targeting motif, serves as a delivery address. The protein is produced outside the mitochondria, and this motif helps ensure that it is delivered to the mitochondria. Another region, called the kinase domain, probably carries out the protein's protective function.


Location :PINK1 gene is present chromosome 1 and coded from 20,832,534 to 20,850,590 region ,the cytogenetic location is 1p36 ,The gene size is 18057 bp with 8 exons.

Disease:
Researchers have identified more than 20 PINK1 mutations that cause early-onset Parkinson disease. Some mutations change one of the protein building blocks (amino acids) used to make PTEN induced putative kinase 1. Other mutations lead to an abnormally small version of the protein. Many PINK1 mutations alter or eliminate the kinase domain, leading to a loss of protein function. At least one mutation affects the mitochondrial-targeting motif and may disrupt delivery of the protein to mitochondria. With reduced or absent PTEN induced putative kinase 1 activity, mitochondria may malfunction, particularly when cells are stressed. Cells can die if power is not provided for essential activities. It is unclear how PINK1 mutations cause the selective death of nerve cells that characterizes Parkinson disease.


Friday, October 24, 2008

PARK7 Gene

The official name of this gene is “Parkinson disease (autosomal recessive, early onset) 7.”PARK7 Gene provides informations to produce DJ-1 protein ,Studies indicate that this protein has several functions like positve regualtor of androgen receptor transcription.The DJ-1 protein helps to protect brain cells (especially neurons)from oxidative stress.Oxidative stress ocurs when unstable molecules called free radicals accumulate to levels that damage or kill cell additionaly it also function as a Chaperone molecule that helps fold newly produced proteins into the proper 3-dimensional shape and helps refold damaged proteins.Researchers also suggest that the DJ-1 protein may play a role in activities that produce and process RNA, a chemical cousin of DNA.


Location :PARK7 gene is present chromosome 1 and coded from 7944380 to 7967926 region ,the cytogenetic location is 1p36.23 ,The gene size is 23547 bp with 7 exons


Disease:

Parkinson disease is caused by mutation in PARK7 gene,reseachers had identified more than 10 PARK7 mutations that cause early-onset Parkinson disease,In some cases large portion of PARK& gene is deleted and no product is produced (functional DJ-1 Protein),other mutations creates an altered protein which doesn not function properly
Understanding Parkinson's Disease


Mode of action:

Some researchers suggest PARK7 mutations distrupt teh proteins chaperone function which leads to a toxic buildup of misfold or damaged proteins and eventually to cell death.Another possibility is that PARK7 mutations impair the protein's ability to protect cells from destructive oxidative stress. Nerve cells that make the chemical messenger dopamine are particularly vulnerable to oxidative stress. With diminished protection, free radicals may cause enough damage to kill these nerve cells. Loss of dopamine-producing nerve cells is a characteristic feature of Parkinson disease.




New Drug Approved by FDA for Parkinson's Disease

Monday, October 20, 2008

MUTYH Gene

Definition: mutY homolog (E. coli)

Official Symbol:MUTYH

Chromosome:1

Location : 1p34.3-p32.1

Gene Size: 11229 bp complement(45567501..45578729)


No Exons:16

Description:
MUTYH gene encodes a MYH glycosylase which is involved in oxidative DNA damage repair,The enzyme corrects mistakes in DNA ,which occur during DNA replication (during cell division),During cell division Guanine(G) sometimes becomes altered by oxygen and gets paired with Adenine(A),M instead of cytosine (C) MYH glycosylase fixes this mistake so mutations do not accumulate in the DNA and lead to tumor formation,This type of repair is known as base excision repair.



Disease :
familial adenomatous polyposis - caused by mutations in the MUTYH gene

Mutations in the MUTYH gene cause an autosomal recessive form of familial adenomatous polyposis (also called MYH-associated polyposis). Mutations in this gene affect the ability of cells to correct mistakes made during DNA replication. In individuals who have autosomal recessive familial adenomatous polyposis, both copies of the MUTYH gene in each cell are mutated. Most mutations in this gene result in the production of a nonfunctional or low-functioning MYH glycosylase. When base excision repair in the cell is impaired, mutations in other genes build up, leading to cell overgrowth and possibly tumor formation. Two mutations that change the sequence of the building blocks of proteins (amino acids) in MYH glycosylase are common in people of European descent. One mutation replaces the amino acid tyrosine with the amino acid cysteine at position 165 (written as Tyr165Cys or Y165C). The other mutation switches the amino acid glycine with the amino acid aspartic acid at position 382 (written as Gly382Asp or G382D).

MTR Gene

Definition:5-methyltetrahydrofolate-homocysteine methyltransferase

Official Symbol:MTR

 Chromosome
:1


Gene Size: 105245 bp   235025341..235130585


No Exons:33

 Location : 1q43
Description:
MTR gene provides information for making an enzyme called methionine synthase.This enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis

Disease :
Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency complementation group G,and Homocystinuria  Disease.In this disease more than 15 mutations in the MTR gene have been identified in people with homocystinuria. Many of these mutations lead to the production of an abnormally small, nonfunctional version of methionine synthase. Other mutations change single amino acids in the enzyme, which disrupts the enzyme's activity. For example, one of the most common mutations replaces the amino acid proline with the amino acid leucine at position 1173 (written as Pro1173Leu or P1173L). Without functional methionine synthase, homocysteine cannot be converted to methionine. As a result, homocysteine builds up in the bloodstream and methionine is depleted. Some of the excess homocysteine is excreted in urine. Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.

Sunday, October 19, 2008

MTHFR Gene

Definition:5,10-methylenetetrahydrofolate reductase (NADPH)

Official Symbol:MTHFR

Chromosome:1


Gene Size: 20329 bp complement(11768374..11788702)


No Exons:12

Location : 1p36.3



Description:
MTHFR gene codes for an enzyme called methylenetetrahydrofolate reductase,which plays vital role in amino acid processing and protein building blocks ,Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine


Disease :
Mutations in the gene MTHFR causes disease called Homocystinuria,Homocystinuria, also known as Cystathionine beta synthase deficiency, is an inherited disorder of the metabolism of the amino acid methionine, often involving cystathionine beta synthase. It is an inherited autosomal recessive trait, About 24 mutation in MTHFR gene have been identified in people with homocystinuria,Most of these mutaions are single amino acids in methylenetetrahydrofolate reductase.These substitutions disrupt the function of the enzyme, and may inactivate it completely,Without methylenetetrahydrofolate reductase, homocysteine cannot be converted to methionine. As a result, homocysteine builds up in the bloodstream and methionine is depleted. Some of the excess homocysteine is excreted in urine. Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.

Homocystinuria, What is it?

Saturday, October 18, 2008

MPZ - Myelin protein zero Gene

Definition:Myelin protein zero

Official Symbol:MPZ

Chromosome:1


Gene Size: 5227 bp (159541151..159546377)



No Exons:6


Location : 1q23.3




Description:
MPZ gene codes for making a protein called myelin protein zero, it is found abundant in the myelin sheath, the covering that protects nerves and promotes the efficient transmission of nerve impulses, Schwann cells are the only cells that produces myelin protein zero, This protein is required for the proper formation and maintenance of myelin, it acts like a molecular glue (adhesion molecule) and plays a role in tightly packing the myelin.

Disease:
Mutations in MPZ gene causes disease like Autosomal dominant form of Charcot-Marie-Tooth disease type 1 and other polyneuropathies, More than 100 mutations in MPZ gene causes a form of Charcot-Marie-tooth known as type 1B,These mutations alter the extracellular domain by replacing one of the building blocks (amino acids) in the myelin protein zero with incorrect amino acid, the altered myelin protein zero probably cannot interact properly with other myelin components, which disrupts the formation and maintenance of the myelin sheath, As a result, peripheral nerve cells cannot activate muscles used for movement or relay information from sensory cells back to the brain, causing the signs and symptoms of type 1B Charcot-Marie-Tooth disease.

MFN2 Mitofusin Gene

Definition:Mitofusin 2

Official Symbol:MFN2

Chromosome:1
Gene Size: 33197 bp (11962956..11996152)



No Exons:19


Location : 1p36.22












Description:This gene codes for a protein called mitofusin 2,This protein helps to determine the shape and structure of mitochondria during fission and fusion,This protein is involved in the regulation of vascular smooth muscle cell proliferation, and it may play a role in the pathophysiology of obesity


Disease :
Mutations in MFN2 gene cause disease like Charcot-Marie-Tooth disease (CMT disease)and Hereditary motor and sensory neuropathy VI,

In Charcot-Marie-Tooth disease Researchers have identified more than 30 MFN2 mutations,Almost all these mutations replace one of the protein building blocks in mitofusin 2 with an incorrect amino acid,As a result the mitofusin 2 protein are altered in critical region and cannot function properly,

Recent research showed that the mutated MFN2 causes mitochondria to form large clusters. In nerve cells these large clusters of mitochondria failed to travel down the axon towards the synapses. It is suggested these mitochondria clots make the synapses fail, resulting in CMT disease

Thursday, October 16, 2008

LMNA Gene

Definition:Lamin A/C


Official Symbol:LMNA

Chromosome:1


Location : 1q21.2-q21.3

Gene Size: 25418 bp (154351085..154376502)


No Exons:12


Description:
The LMNA gene provides instructions for making several slightly different proteins called lamins. The two major proteins produced from this gene, lamin A and lamin C, are made in most of the body's cells. These proteins have a nearly identical sequence of protein building blocks (amino acids). The small difference in the sequence makes lamin A longer than lamin C.The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Through alternate splicing, this gene encodes three type A lamin isoforms. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy,



Disease :
Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford progeria syndrome
Mutation in the LMNA gene has been found in most patients with Hutchinson-Gilford progeria syndrome The G608G mutation in exon 11 of the LMNA gene is present in all individuals with HGPS,mutation changes a single DNA building block (nucleotide) in the gene. Specifically, the mutation replaces the nucleotide cytosine with the nucleotide thymine at position, This mutation is also sometimes noted as Gly608Gly or G608G, which refers to the position in the lamin A protein affected by the mutation. The C1824T mutation leads to an abnormal version of the lamin A protein called progerin, which is missing 50 amino acids near one end. The location of this mutation does not affect the production of lamin C. Other mutations in the LMNA gene have been identified in a small number of people with the features of Hutchinson-Gilford progeria syndrome.


The mutations responsible for this disorder result in an abnormal version of lamin A that cannot be processed correctly within the cell. When the altered protein is incorporated into the lamina, it can disrupt the shape of the nuclear envelope. Over time, a buildup of this altered protein appears to damage the structure and function of the nucleus, making cells more likely to die prematurely. Researchers are working to determine how these changes lead to the signs and symptoms of Hutchinson-Gilford progeria syndrome.

KIF1B Gene

Definition:Kinesin family member 1B


Official Symbol:KIF1B

 Chromosome:1


 Location : 1p36.2


Gene Size: 170825 bp (REGION: 10193418..10364242)


No Exons:47

Description:
This gene encodes a motor protein that transports mitochondria and synaptic vesicle precursors.These proteins are essential for the transport of materials within cells. Kinesin proteins function like freight trains that transport cargo, and their structure is suited for this cargo-carrying function. One part of the protein, called the motor domain, powers the protein and its cargo along a track-like system made from structures called microtubules. Another part of the kinesin protein, which varies among family members, binds to specific materials for transport.
Kinesin Transport Protein


Disease :
Mutations in this gene cause a, type 2A1.One KIF1B gene mutation has been detected in some patients with a form of Charcot-Marie-Tooth disease known as type 2A. The mutation changes one of the protein building blocks (amino acids) in the motor domain of kinesin family member 1B. Specifically, the amino acid glutamine is replaced by the amino acid leucine at protein position 98 (written as Gln98Leu). Although the effect of this mutation is not fully understood, the motor function of the protein and the transport of synaptic vesicles are probably disrupted. Lowered levels of synaptic vesicles at nerve endings could impair the transmission of nerve impulses, causing the symptoms of type 2A Charcot-Marie-Tooth disease.

Wednesday, October 15, 2008

KCNQ4 Gene

Definition: Potassium voltage-gated channel, KQT-like subfamily, member 4

Official Symbol:KCNQ4

 Chromosome:1

 Location
: 1p34

Gene Size
: 54677 bp (41022271..41076947)


No Exons
:14


Description
:
The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The current generated by this channel is inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene,Potassium channels made with the KCNQ4 protein are found in the inner ear and along part of the nerve pathway from the ear to the brain (auditory pathway). KCNQ4 potassium channels are also found in small numbers in the heart and some muscles.

Disease :
Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene.

Nonsyndromic deafness - caused by mutations in the KCNQ4 gene

    Several KCNQ4 mutations have been reported in individuals with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNA2. Most KCNQ4 mutations change one of the building blocks (amino acids) used to make the KCNQ4 protein. Nearly all of these changes affect the region of the protein that forms the pore or channel opening. As a result, the channel does not function properly and normal potassium ion levels may be disturbed. Two mutations delete part of the KCNQ4 gene, which results in an abnormally small KCNQ4 protein that cannot form functional channels. It is unclear whether deafness results from disturbed potassium levels within the inner ear, alterations in the auditory pathway, or both.

IRF6 Gene

Definition:Interferon regulatory factor 6


Official Symbol:IRF6


 Chromosome:1


 Location : 1q32.3-q41


Gene Size: 18218 bp complement(208027885..208046102)


No Exons: 9

Description:
This gene encodes a member of the interferon regulatory transcription factor (IRF) family. Family members share a highly-conserved N-terminal helix-turn-helix DNA-binding domain and a less conserved C-terminal protein-binding domain.

Disease :
Mutations in this gene can cause van der Woude syndrome and popliteal pterygium syndrome. This protein is involved in palate formation.A shortage of the IRF6 protein affects the development and maturation of tissues in the skull and face. These abnormalities underlie the signs and symptoms of van der Woude syndrome, including cleft lip, cleft palate (an opening in the roof of the mouth), and pits or mounds in the lower lip.


Popliteal Pterygium syndrome
Mutations in the IRF6 gene that cause popliteal pterygium syndrome may change the transcription factor's effects on the activity of certain genes. This affects the development and maturation of tissues in the face, skin, and genitals, resulting in the facial and genital abnormalities, skin webbing, and fusion of the fingers or toes (syndactyly) seen in popliteal pterygium syndrome.

RNASEL Gene

Defintion:Ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent)

Official Symbol:RNASEL

 Chromosome:1


 Location : 1q25

Gene Size: 13337 BP complement(155654005..155667341)



No Exons: 6


Description:
This gene encodes a component of the interferon-regulated 2-5A system that functions in the antiviral and antiproliferative roles of interferons. Mutations in this gene have been associated with predisposition to prostate cancer and this gene is a candidate for the hereditary prostate cancer 1 (HPC1) allele. [provided by RefSeq]



Disease :
RNase L is part of the body's innate immune defense, namely the antiviral state of the cell. When a cell is in the antiviral state, it is highly resistant to viral attacks and is also ready to undergo apoptosis upon successful viral infection. Degradation of all RNA within the cell (which usually occurs with cessation of translation activity caused by protein kinase R is the cell's last stand against a virus before it attempts apoptosis.

Prostate Cancer - Radical Prostatectomy

HMGCL Gene

Defintion:3-hydroxymethyl-3-methylglutaryl-Coenzyme

Official Symbol:HMGCL

 Chromosome:1

 Location : 1p36.1-p35

Gene Size: 23583 bp complement(24000954..24024536)


No Exons
: 9

Description:
The HMGCL gene provides instructions for making an enzyme that is found in mitochondria (the energy-producing centers inside cells). This enzyme, called 3-hydroxymethyl-3-methylglutaryl-coenzyme A (CoA) lyase, plays an essential role in breaking down proteins and fats from the diet. Specifically, 3-hydroxymethyl-3-methylglutaryl-CoA lyase is needed to process leucine, an amino acid used as a building block in many enzymes and other proteins. This enzyme is also involved in making ketones when fat is broken down by the body. These reactions produce molecules that are later used for energy.


Disease :
Many of the identified HMGCL mutations change the amino acids used as building blocks in the enzyme 3-hydroxymethyl-3-methylglutaryl-CoA lyase. Other mutations cause the production of an abnormally shortened enzyme that is missing critical components. All of these mutations disrupt the normal function of 3-hydroxymethyl-3-methylglutaryl-CoA lyase. As a result, leucine cannot be processed and ketones cannot be made properly. Because of incomplete processing, certain chemical byproducts (organic acids) can build up and cause the blood to become too acidic (metabolic acidosis). In addition, a lack of ketones causes blood sugar to become dangerously low (hypoglycemia). The effects of metabolic acidosis and hypoglycemia can damage the brain and nervous system.