title: A novel human sex-determining gene linked to Xp11.21-11.23.
abstract: BACKGROUND
  The molecular basis for about 70-80% of 46,XY sex-reversed females remains unexplained, because they carry normal copies of the genes (SRY, SOX9, DAX1, DMRT, SF1, WT1) involved in sex determination pathway.
  
  
  OBJECTIVE
  The objective of this study is to map the chromosomal locus responsible for an unexplained sex-reversed phenotype.
  
  
  METHODS
  The study implemented a genome-wide scan using families with multiple sex-reversed individuals.
  
  
  METHODS
  The patients, along with the family members, were selected from different hospitals/reproductive centers.
  
  
  METHODS
  Sex-reversed individuals and their siblings and parents participated in the study.
  
  
  METHODS
  Identification of the chromosomal locus responsible for sex reversal in these families and sequence analysis of candidate genes were the main outcome measures.
  
  
  RESULTS
  Parametric linkage analysis revealed a maximum two-point LOD score of 5.70 with marker DXS991 (Xp11.21) and 4.57 with marker DXS1039 (Xp11.23-Xp11.22), and a multipoint LOD score of 5.77 with marker DXS991 and 5.22 with marker DXS1039. The two markers (DXS991 and DXS1039) with highest LOD score span approximately 3.41 cM (75.79-79.2 cM) on the short arm of the X-chromosome.
  
  
  CONCLUSIONS
  Our findings provide evidence for a major susceptibility locus for sex reversal/gonadal dysgenesis on the short arm of the X-chromosome (Xp11.21-11.23). Furthermore, molecular exploration of the expression of candidate genes in the embryonic gonad/gonadal ridge will help in the identification of the underlying gene for sex reversal.
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Singh
authors.initials: S
authors.lastname: Rajender
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
authors.forename: Nalini J
authors.initials: NJ
authors.lastname: Gupta
authors.forename: N
authors.initials: N
authors.lastname: Leelavathy
authors.forename: Deepa Selvi
authors.initials: DS
authors.lastname: Rani
authors.forename: Renjini G
authors.initials: RG
authors.lastname: Nambiar
authors.forename: Vadivelu
authors.initials: V
authors.lastname: Kalavathy
authors.forename: Sathiyavedu T
authors.initials: ST
authors.lastname: Santhiya
authors.forename: Sayee
authors.initials: S
authors.lastname: Rajangam
authors.forename: Puthiya M
authors.initials: PM
authors.lastname: Gopinath
authors.forename: Baidyanath
authors.initials: B
authors.lastname: Chakravarty
authors.forename: Lalji
authors.initials: L
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D012734:Disorders of Sex Development; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D019849:Sex Determination Processes