Alternative mechanisms of genetic

Alternative mechanisms of genetic transmission Anticipation Anticipation is present in genetic diseases when successive generations have earlier onset of illness, greater severity, and/or greater likelihood of being affected. Once the mechanism of expanding trinucleotide repeats (TNRs) was discovered in fragile-X mental retardation, and then in a succession of other neuropsychiatrie

diseases, including Huntington’s disease and several spinocerebellar atrophies, investigators began a scrutiny of BP and SZ for anticipation and for expanding TNRs.79 At present, observations consistent with anticipation are being repeatedly reported, although there is some question as to whether this is Inhibitors,research,lifescience,medical a birth-cohort effect or ascertainment artifact, as reviewed elsewhere.80-83 Inhibitors,research,lifescience,medical There have been some claims of expanding repeats Dorsomorphin 1219168-18-9 associated with major psychiatric illness, including an association with childhood-onset SZ,84 but nearly all of these repeats have subsequently been shown to be common polymorphisms not Inhibitors,research,lifescience,medical associated with disease, as reviewed elsewhere.85 However, there

remains some possibly diseaseassociated TNRs that merit further investigation.86 Aneuploidal events VCFS is associated with deletions in a region on the q arm of chromosome 22, including microdeletions, and with psychiatric manifestations of BP and SZ.85-87 Many other aneuploidal events have been found in isolated cases or families with BP or SZ, but the finding on chromosome 22 is the most frequent. The region Inhibitors,research,lifescience,medical of reported linkage to these disorders on the q arm

of chromosome 22 is consistent with the finding of microdeletions. The gene for catechol – O-methyltransf erase (COMT) is within the deletion region for VCFS. Modest evidence for an association of COMT with SZ has been reported,90-92 but other studies do not find any evidence for association in SZ93,94 or in BP95 Sex-of-parent-Sunitinib FLT3 specific transmission BP has been reported to have excess maternal transmission,96,97 and Inhibitors,research,lifescience,medical some linkages appear to be specific to AV-951 paternal or maternal history.96-98 There has not been great consistency in these observations,99,100 but there are enough repeated findings to consider mechanisms that might be implicated. An associated mitochondrial variant has not appeared consistently.101,102 Imprinting has not been sufficiently investigated for comment. Malaspina has presented data showing that sporadic cases of SZ are associated with increased paternal age, but not increased maternal age, implying that new mutations may be playing a role.103 Periodic catatonia, a form of SZ, had a paternal parent-of-origin effect associated with early onset in one series.104 Candidate genes In contrast to linkage, associations do not yet have an agreed-upon criterion for genome-wide significance.

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