Microcephalin: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
some people with microcephaly are perfectly normal
PLEASE READ DISCUSSION-MISLEADING CLAIMS-
Line 131: Line 131:
| LocusSupplementaryData =
| LocusSupplementaryData =
}}
}}
The '''''microcephalins''''' ([[Greek language|Greek]] for "small head") are a group of six genes (called ''MCPH1'' to ''MCPH6''), in which two copies of a loss-of-function mutation causes primary [[microcephaly]] ({{OMIM|251200}}), a condition characterised by a severely diminished [[human brain|brain]].<ref>
Autosomal recessive primary microcephaly ([[Greek language|Greek]] for "small head"), or MCPH ({{OMIM|251200}}), is a developmental disorder characterized by a severely reduced [[human brain|brain]] size present at birth with subsequent mental retardation. At least six [[locus (genetics)|loci]] have been linked to MCPH; the responsible genes (called ''MCPH1'' to ''MCPH6'') have been identified for four of these loci. It is hypothesized that these genes play a role in brain development and were necessary for the evolution of human brain size (for review, see Woods et. al. 2005<ref>
{{cite journal
{{cite journal
| author = Woods, C.G., ''et al.''
| author = Woods, C.G., ''et al.''
Line 141: Line 141:
| url = http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15806441
| url = http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15806441
| pmid = 15806441}}
| pmid = 15806441}}
</ref>). Evidence suggesting MCPH1 and ASPM (MCPH5) underwent strong positive selection during human evolution has prompted several cognitive ability studies of humans possessing different variants of these genes; however, this evidence has been refuted by others <ref>
</ref> Hence it has been assumed that normal variants of the these genes have a role in brain development, but evidence to support this is lacking so far.<ref>
{{cite journal
{{cite journal
| author = Evans, P.D., ''et al.''
| author = Evans, P.D., ''et al.''

Revision as of 23:57, 2 September 2007

microcephaly, primary autosomal recessive 1
Identifiers
SymbolMCPH1
Alt. symbolsMicrocephalin[1], BRIT1[2]
NCBI gene79648
HGNC6954
OMIM607117
UniProtQ8NEM0
Other data
LocusChr. 8 p23
Search for
StructuresSwiss-model
DomainsInterPro
microcephaly, primary autosomal recessive 2
Identifiers
SymbolMCPH2
NCBI gene4181
HGNC6955
OMIM604317
Other data
LocusChr. 19 q13.1-13.2
microcephaly, primary autosomal recessive 3
Identifiers
SymbolCDK5RAP2
Alt. symbolsMCPH3
NCBI gene23702
HGNC6956
OMIM604804
Other data
LocusChr. 9 q33.3
microcephaly, primary autosomal recessive 4
Identifiers
SymbolMCPH4
NCBI gene23701
HGNC6957
OMIM604321
Other data
LocusChr. 15 q15-21
microcephaly, primary autosomal recessive 5
Identifiers
SymbolASPM
Alt. symbolsMCPH5
NCBI gene64590
HGNC6958
OMIM608716
Other data
LocusChr. 1 q31
microcephaly, primary autosomal recessive 6
Identifiers
SymbolCENPJ
Alt. symbolsMCPH6
NCBI gene170629
HGNC17120
OMIM608393
Other data
LocusChr. 13 q12.2

Autosomal recessive primary microcephaly (Greek for "small head"), or MCPH (Online Mendelian Inheritance in Man (OMIM): 251200), is a developmental disorder characterized by a severely reduced brain size present at birth with subsequent mental retardation. At least six loci have been linked to MCPH; the responsible genes (called MCPH1 to MCPH6) have been identified for four of these loci. It is hypothesized that these genes play a role in brain development and were necessary for the evolution of human brain size (for review, see Woods et. al. 2005[3]). Evidence suggesting MCPH1 and ASPM (MCPH5) underwent strong positive selection during human evolution has prompted several cognitive ability studies of humans possessing different variants of these genes; however, this evidence has been refuted by others [4] [5] [6].

Expression in the brain

MCPH1 is expressed in the fetal brain, in the developing forebrain, and on the walls of the lateral ventricles. Cells of this area divide, producing neurons that migrate to eventually form the cerebral cortex.

Evolution

A derived form of MCPH1 called haplogroup D appeared about 37,000 years ago (anytime between 14,000 and 60,000 years ago) and has spread to become the more common form throughout the world except Sub-Saharan Africa. The timing of its emergence may have closely preceded the Upper Paleolithic, when people started colonising Europe, although the margin of error is substantial[7] and there is evidence that the transition to the Upper Paleolithic occurred in Africa before spreading to Europe.[8] Doubts concerning origins aside, modern distributions of chromosomes bearing the ancestral forms of MCPH1 and MCPH5 coincide with the incidence of tonal languages, although the nature of this relationship can only be guessed at.[9]

Haplogroup D may have originated from a lineage separated from modern humans approximately 1.1 million years ago and later introgressed into humans. This finding supports the possibility of admixture between modern humans and extinct Homo spp. (Neanderthals being one possibility).[10] On the other hand the sample of 89 individuals with only nine Africans used in the study has been criticized as being inadequate for the conclusion the paper draws, and comparable studies demonstrate that undersampling specific areas of East/Central Africa may lead to unwarranted conclusions.[11] Additionally, scientists have not identified the evolutionary pressures that caused the supposed spread of these mutations.[12]

Controversy

Although Chinese himself, Bruce Lahn's public announcements some brain-genes are more advanced on some continents than on others were conscripted by websites promoting white "racialism". An American xenophobic magazine embraced the research as "the moment the antiracists and egalitarians have dreaded." The National Review Online, wrote that as a result of the findings, "our cherished national dream of a well-mixed and harmonious meritocracy may be unattainable."

Lahn's study began to attract considerable controversy in the science world, where he was criticized for overinterpreting and sensationalizing his findings. One of the co-authors, Sarah Tishkoff, distanced herself from the study saying that she was bothered how the paper drew a link between the genetic changes and the rise of civilization. She felt that any conclusions about why the mutations spread were premature and that it is "very simplistic" to confer so many behavioural traits on a single gene. Richard Lewontin considers the two published papers as "egregious examples of going well beyond the data to try to make a splash." All the while maintaining that the science of his studies were sound, Lahn has nevertheless conceded that there is no real evidence natural selection had acted on cognition or intelligence through the genes. Tainted by the experience, he is engaging himself with other areas of study.[13][14]

Other names

The microcephaly-related genes MCPH 3, 5 and 6 are usually classified by their alternate names CDK5RAP2, ASPM and CENPJ respectively, according to their other roles. (More information can be found from the articles dedicated to them and links in the information boxes.)

See also

References

  1. ^ Jackson, A.P.; et al. (2002). "Identification of Microcephalin, a Protein Implicated in Determining the Size of the Human Brain". Am. J. Hum. Genet. 71: 136–142. PMID 12046007. {{cite journal}}: Cite has empty unknown parameter: |1= (help); Explicit use of et al. in: |author= (help)
  2. ^ Lin, S.Y. & Elledge, S.J. (2003). "Multiple tumor suppressor pathways negatively regulate telomerase". Cell. 113: 881–889. PMID 12837246.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Woods, C.G.; et al. (2005). "Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings". Am. J. Hum. Genet. 76: 717–728. PMID 15806441. {{cite journal}}: Explicit use of et al. in: |author= (help)
  4. ^ Evans, P.D.; et al. (2004). "Reconstructing the evolutionary history of microcephalin, a gene controlling human brain size". Human Molecular Genetics. 13: 1139–1145. PMID 15056607. {{cite journal}}: Explicit use of et al. in: |author= (help)
  5. ^ Evans, P.D.; et al. (2004). "Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans". Human Molecular Genetics. 13: 489–494. PMID 14722158. {{cite journal}}: Explicit use of et al. in: |author= (help)
  6. ^ Timpson, N.; et al. (2007). "Comment on papers by Evans et al. and Mekel-Bobrov et al. on Evidence for Positive Selection of MCPH1 and ASPM". Science. 317: 1036. PMID 17717170. {{cite journal}}: Explicit use of et al. in: |author= (help)
  7. ^ Evans, P.D.; et al. (2005). "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans". Science. 309: 1717–20. doi:10.1126/science.1113722. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)
  8. ^ Ambrose, S.H. (1998). "Chronology of the Later Stone Age and food production in East Africa". J. Archaeol. Sci. 25 (4): 377–392. doi:10.1006/jasc.1997.0277. {{cite journal}}: Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)
  9. ^ Dediu, D. & D.R. Ladd (2007). "Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin". Proc. Nat. Acad. Sci. doi:10.1073/pnas.0610848104.
  10. ^ PNAS article Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage Published online before print November 7, 2006 by Proceedings of the National Academy of Sciences of the USA
  11. ^ Shimada MK, Panchapakesan K, Tishkoff SA, Nato AQ, Hey J (2007). "Divergent haplotypes and human history as revealed in a worldwide survey of X-linked DNA sequence variation". Mol. Biol. Evol. 24 (3): 687–98. doi:10.1093/molbev/msl196. PMID 17175528.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Mekel-Bobrov, N.; et al. (2007). "The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence". Hum. Mol. Genet.: adv. access. doi:10.1093/hmg/ddl487. {{cite journal}}: Explicit use of et al. in: |author= (help)
  13. ^ scientists study of brain gene sparks a backlash
  14. ^ Balter, M. (2006). "Bruce Lahn profile: Brain man makes waves with claims of recent human evolution". Science. 314 (5807): 1871–1873. doi:10.1126/science.314.5807.1871. {{cite journal}}: Unknown parameter |month= ignored (help)

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Microcephalin&oldid=155308786"