High impact information on ASPM

• Indeed, evolutionary analyses of Microcephalin and ASPM reveal evidence for positive selection during human and great ape evolution [1].
• We now report a fifth locus, MCPH5, which is an 8-cM region mapping to chromosome 1q31, defined by the markers GATA135F02 and D1S1678 [2].
• Primary autosomal recessive microcephaly: MCPH5 maps to 1q25-q32 [3].
• We report homozygosity mapping of a new locus, MCPH5, with a maximum multipoint LOD score of 3.51 at marker D1S1723, in a family of Turkish origin [3].
• Immunostaining of cultured human cells with antibodies revealed that ASPM is localized in the spindle poles during mitosis [4].

Biological context of ASPM

• MCPH1 and ASPM both have very young single nucleotide polymorphism haplotypes associated with modern humans, and these genes are presumably still evolving in Homo sapiens [5].
• Whereas aberration of ASPM is the most common cause of MCPH, MCPH1 patients can be more readily diagnosed by the finding of increased numbers of 'prophase-like cells' on routine cytogenetic investigation [6].
• DNA-sequence analysis identified one known (Arg117X) and two novel (Trp1326X and Gln3060X) mutations in the three MCPH5-linked families in a homozygous state [7].
• Our observation adds to the mutation spectrum of ASPM in primary microcephaly, and is to our knowledge the second example of a constitutional, reciprocal translocation responsible for a bona fide autosomal recessive phenotype [8].
• Haplotype analysis suggests that the gene causing microcephaly is located between markers D1S3469 and D1S1660, which excludes the previously reported ASPM gene [9].

Anatomical context of ASPM

• One of its causative genes, ASPM, might play an important role in regulating proliferation of neuronal progenitor cells [10].
• The extensive expression of multiple IQ-motif genes and the absence of ASPM in nondividing adult brain and skeletal muscle also suggest a role in cell division [11].
• ASPM localizes to the centrosome in interphase and to the spindle poles from prophase through telophase [12].

Other interactions of ASPM

• Genetic analysis of primary microcephaly in Indian families: novel ASPM mutations [7].
• The results were suggestive of linkage of three families to the MCPH5 locus and one family to the MCPH2 locus [7].
• Here, we report that downregulation of endogenous ASPM by siRNA decreases protein levels of endogenous BRCA1 [12].

References