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].

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.