Читать книгу Handbook of Clinical Gender Medicine - Группа авторов - Страница 112

Male-limited expression of genes on the Y chromosome can also produce biased sex ratios. This possibility has attracted very little research attention. Such genes should be located in the nonrecombining region of the Y chromosome. SRY (the sex-determining gene) is expressed in the medial rostral hypothalamus, as well as the frontal and temporal regions of the human brain. In vitro assays suggest that SRY can increase transcription of tyrosine hydroxylase (the rate-limiting enzyme in dopamine biosynthesis). In addition, the knockdown of SRY expression in the substantia nigra of the rat decreases tyrosine hydroxylase expression [see 4 for review]. SRY may also regulate monoamine oxidase A (MAO-A) [4] and brain β-endorphin levels [29]. Other Y-linked genes known to be expressed in the human brain include ZFY and PCDH11Y. A small candidate gene study failed to find associations between variants in PCDH11Y and autism, while ZFY and SRY have not been specifically investigated. Comparison of Y chromosome haplotype groups between cases and controls represents an alternative strategy for identifying Y chromosome effects. Two such studies have been conducted with regard to ASC – one was positive and one was negative [see 4 for review].

As noted previously, XYY and XXYY males are at an increased risk for ASC, which would be compatible with a role for the Y chromosome. However, it should be noted that an increased risk for ASC may also be present in individuals with Klinefelter syndrome (XXY) which could implicate a pseudoautosomal locus on the sex chromosomes in the etiology of ASC, but this would not necessarily help explain the male bias (as pseudoautosomal regions should act like nonsex chromosomes). Y chromosome effects certainly merit additional research attention, but current evidence is insufficient to determine whether this mechanism could explain the sex bias in ASC.