A gene involved in XY sex reversal is located on chromosome 9, distal to marker D9S1779
A gene involved in XY sex reversal is located on chromosome 9, distal to marker D9S1779
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DOI：
10.1086/302016
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发表时间：
1998-09-01
影响因子：
9.8
通讯作者：
Chandrasekharappa, S
中科院分区：
文献类型：
--
作者：
Flejter, WL;Fergestad, J;Chandrasekharappa, S
性别分化的遗传机制知之甚少，相关基因的鉴定进展缓慢。偶然发现的染色体重排与性别逆转表型相关，导致SRY和SOX 9的分离，两者都被证明参与性别决定途径。此外，X染色体的复制、9号和10号染色体的缺失以及涉及17号染色体的易位已被报道与异常睾丸分化相关，导致46，XY个体的男性到女性的性反转。我们提出的细胞遗传学和分子分析的四个性别逆转XY女性，每个性腺发育不全和其他变量畸形，并与末端缺失的远端染色体9p，导致不平衡的常染色体易位。SRY的PCR扩增和DNA序列分析显示在高迁移率组结构域中没有突变（即，HMG盒）中的任何一个。常规和分子细胞遗传学分析中期染色体从每个病人的建议，最小的重叠区域（SRO）的缺失涉及一个非常小的区域的远端带9p24。使用17个高度多态性微卫星标记的杂合性丢失研究，以及使用YAC克隆对应于9p上最远端标记的FISH，表明SRO位于标记D9S1779的远端。这些结果显着缩小了假定的性别决定基因的最末端区域的短臂的9号染色体。
The genetic mechanisms involved in sex differentiation are poorly understood, and progress in identification of the genes involved has been slow The fortuitous finding of chromosomal rearrangements in association with a sex-reversed phenotype has led to the isolation of SRY and SOX9, both shown to be involved in the sex-determining pathway. In addition, duplications of the X chromosome, deletions of chromosomes 9 and 10, and translocations involving chromosome 17 have been reported to be associated with abnormal testicular differentiation, leading to male-to-female sex reversal in 46,XY individuals. We present the cytogenetic and molecular analyses of four sex-reversed XY females, each with gonadal dysgenesis and other variable malformations, and with terminal deletions of distal chromosome 9p, resulting from unbalanced autosomal translocations. PCR amplification and DNA sequence analysis of SRY revealed no mutations in the high-mobility-group domain (i.e., HMG box) in any of the four patients. Conventional and molecular cytogenetic analyses of metaphase chromosomes from each patient suggest that the smallest region of overlap (SRO) of deletions involves a very small region of distal band 9p24. Loss-of-heterozygosity studies using 17 highly polymorphic microsatellite markers, as well as FISH using YAC clones corresponding to the most distal markers on 9p, showed that the SRO lies distal to marker D9S1779. These results significantly narrow the putative sex-determining gene to the very terminal region of the short arm of chromosome 9.