Tag Archives: MCPH1

ASPM and MCPH1 and intelligence not linked.

The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence.

Mekel-Bobrov N, Posthuma D, Gilbert SL, Lind P, Gosso MF, Luciano M, Harris SE, Bates TC, Polderman TJ, Whalley LJ, Fox H, Starr JM, Evans PD, Montgomery GW, Fernandes C, Heutink P, Martin NG, Boomsma DI, Deary IJ, Wright MJ, de Geus EJ, Lahn BT.

Department of Human Genetics, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.

Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental disorder characterized by severe reduction in brain size and intelligence, reminiscent of the early hominid condition. This has led to the hypothesis that the adaptive evolution of these genes has contributed to the emergence of modern human cognition. As with other candidate loci, however, this hypothesis remains speculative due to the current lack of methodologies for characterizing the evolutionary function of these genes in humans. Two primary microcephaly genes, ASPM and Microcephalin, have been implicated not only in the adaptive evolution of the lineage leading to humans, but in ongoing selective sweeps in modern humans as well. The presence of both the putatively adaptive and neutral alleles at these loci provides a unique opportunity for using normal trait variation within humans to test the hypothesis that the recent selective sweeps are driven by an advantage in cognitive abilities. Here, we report a large-scale association study between the adaptive alleles of these genes and normal variation in several measures of IQ. Five independent samples were used, totaling 2393 subjects, including both family-based and population-based datasets. Our overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter the post-genomic era, with the number of candidate loci underlying human evolution growing rapidly, our findings highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.

Another brain function and DNA study

Recently-derived variants of brain-size genes ASPM, MCPH1, CDK5RAP and BRCA1 not associated with general cognition, reading or language

Timothy C. Batesa, b, , , Michelle Lucianoa, Penelope A. Lindb, Margaret J. Wrightb, Grant W. Montgomeryb and Nicholas G. Martinb aDepartment of Psychology, University of Edinburgh, UK bQueensland Institute of Medical Research, Australia

Received 11 September 2007;  revised 1 February 2008;  accepted 9 April 2008.  Available online 16 May 2008.

Abstract
Derived changes in genes associated with primary microcephaly (MCPH) have been suggested to be “currently sweeping to fixation” i.e., increasing in frequency in most populations, with the likely outcome that the derived allele will completely displace the ancestral allele over time. Possible causes for this sweep include effects on human reasoning and language. Here we test the hypothesis that these derived alleles are associated with current variation in spoken or written language and related traits. The association of derived alleles of the ASPM, MCPH1, CDK5RAP2 and BRCA1 genes was tested against well-validated measures of dyslexia, specific language impairment, working memory, IQ, and head-size in a family-based association study of over 1776 subjects from 789 families of twins. No evidence for association was found for any gene to any trait. The results strongly did not support the hypothesis that derived alleles in MCPH-related genes are related to the evolution of human language or cognition. Results were compatible with the alternate hypothesis, suggesting that adaptations in these genes associated with a dramatic increase in brain size have long since reached fixation and are now maintained by stabilizing selection.

Which kind of contradicts the last one at least a bit.

A common SNP of MCPH1 is associated with cranial volume variation in Chinese population

A common SNP of MCPH1 is associated with cranial volume variation in Chinese population

Jin-kai Wang1,2,4, Yi Li3 and Bing Su1,2,*
1 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology 2 Kunming Primate Research Centre, Chinese Academy of Sciences, Kunming, Yunnan, PR China 3 Department of Chemistry and Life Science, Qujing Normal University, Qujing, Yunnan, PR China 4 Graduate School of Chinese Academy of Sciences, Beijing, PR China

Received November 17, 2007; Revised December 23, 2007; Accepted January 16, 2008

Microcephaly (MCPH) genes are informative in understanding the genetics and evolution of human brain volume. MCPH1 and abnormal spindle-like MCPH associated (ASPM) are the two known MCPH causing genes that were suggested undergone recent positive selection in human populations. However, previous studies focusing only on the two tag single nucleotide polymorphisms(SNPs) of MCPH1 and ASPM failed to detect any correlation between gene polymorphisms and variations of brain volume and cognitive abilities. We conducted an association study on eight common SNPs of MCPH1 and ASPM in a Chinese population of 867 unrelated individuals. We demonstrate that a non-synonymous SNP (rs1057090, V761A in BRCA1 C-terminus (BRCT) domain) of MCPH1 other than the two known tag SNPs is significantly associated with cranial volume in Chinese males. The haplotype analysis confirmed the association of rs1057090 with cranial volume, and the homozygote males containing the derived alleles of rs1057090 have larger cranial volumes compared with those containing the ancestral alleles. No recent selection signal can be detected on this SNP, suggesting that the brain volume variation in human populations is likely neutral or under very weak selection in recent human history.

I don’t know if it makes the brain any bigger or better though. Although, I’ve seen a few studies that positively correlate brain size and IQ from MRI scans.