A gene involved in XY sex reversal is located on chromosome 9, distal to marker D9S1779

被引:77
作者
Flejter, WL
Fergestad, J
Gorski, J
Varvill, T
Chandrasekharappa, S
机构
[1] Univ Utah, Dept Pediat, Salt Lake City, UT USA
[2] Univ Utah, Dept Human Genet, Salt Lake City, UT USA
[3] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
[5] NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1086/302016
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页码:794 / 802
页数:9
相关论文
共 34 条
[11]   MULTICOLOR FISH MAPPING WITH ALU-PCR-AMPLIFIED YAC CLONE DNA DETERMINES THE ORDER OF MARKERS IN THE BRCA1 REGION ON CHROMOSOME-17Q12-Q21 [J].
FLEJTER, WL ;
BARCROFT, CL ;
GUO, SW ;
LYNCH, ED ;
BOEHNKE, M ;
CHANDRASEKHARAPPA, S ;
HAYES, S ;
COLLINS, FS ;
WEBER, BL ;
GLOVER, TW .
GENOMICS, 1993, 17 (03) :624-631
[12]   CAMPOMELIC DYSPLASIA AND AUTOSOMAL SEX REVERSAL CAUSED BY MUTATIONS IN AN SRY-RELATED GENE [J].
FOSTER, JW ;
DOMINGUEZSTEGLICH, MA ;
GUIOLI, S ;
KWOK, C ;
WELLER, PA ;
STEVANOVIC, M ;
WEISSENBACH, J ;
MANSOUR, S ;
YOUNG, ID ;
GOODFELLOW, PN ;
BROOK, JD ;
SCHAFER, AJ .
NATURE, 1994, 372 (6506) :525-530
[13]  
FRYNS JP, 1986, ANN GENET-PARIS, V29, P49
[14]  
Furlong Robert A., 1992, Human Molecular Genetics, V1, P447, DOI 10.1093/hmg/1.6.447
[15]  
Guioli S, 1997, ANN HUM GENET, V61, P212
[16]   MUTATIONAL ANALYSIS OF SRY - NONSENSE AND MISSENSE MUTATIONS IN XY SEX REVERSAL [J].
HAWKINS, JR ;
TAYLOR, A ;
BERTA, P ;
LEVILLIERS, J ;
VANDERAUWERA, B ;
GOODFELLOW, PN .
HUMAN GENETICS, 1992, 88 (04) :471-474
[17]  
HOO J J, 1989, American Journal of Human Genetics, V45, pA78
[18]   A HUMAN XY FEMALE WITH A FRAME SHIFT MUTATION IN THE CANDIDATE TESTIS-DETERMINING GENE SRY [J].
JAGER, RJ ;
ANVRET, M ;
HALL, K ;
SCHERER, G .
NATURE, 1990, 348 (6300) :452-454
[19]   NEW CASE OF TRISOMY FOR DISTAL PART OF 13Q DUE TO MATERNAL TRANSLOCATION, T(9-13)(P21-Q21) [J].
JOTTERAND, M ;
JUILLARD, E .
HUMAN GENETICS, 1976, 33 (03) :213-222
[20]  
KWOK C, 1995, AM J HUM GENET, V57, P1028