Missing heritability perhaps not how has the human

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Unformatted text preview: eletions, microduplications; etc). Rare copy number variations? Science 2008, 320:542 Not-so rare SNPs, but lots of them ? Missing heritability? Perhaps not… How has the human genome come to have such a great amount of CNV? ! ! Two recombination-based mechanisms, i.e., nonallelic homologous recombination (NAHR) and nonhomologous end-joining (NHEJ) (98), and retrotransposition (63, 64, 68, 181), have been implicated in genomic rearrangements and the formation of CNVs. Recently, a novel replicationbased mechanism, fork stalling and template switching (FoSTeS), has been pro-posed to account for the observed complex genomic rearrangements that cannot be readily explained by NAHR, NHEJ, or retrotransposition (78). Notably, breakpoint sequencing data also suggest that a portion of CNV likely occurs by a mechanism consistent with FoSTeS (125). Ann Rev Genomics Human Genetics 2009, 10, 451-481 !23 Question Think about this, and pick one answer that you believe is most likely true, or go for e and speak up: Why are there so many vulnerability genes for schizophrenia? a) because the real genetic culprit has not yet been found. b) because schizophrenia is very heterogeneous disorder, many different diseases, indeed. c) because minor developmental abnormalities in forebrain neuronal circuitry can cause schizophrenia d) I haven’t the foggiest. e) I have a better idea that I will explain to the class in a minute (please do so)....
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