A CANDIDATE GENE STUDY AND A FULL GENOME SCREEN FOR MALE HOMOSEXUALITY

Open Access
Author:
DuPree, Michael Glenn
Graduate Program:
Anthropology
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
July 15, 2002
Committee Members:
  • Kenneth Monrad Weiss, Committee Member
  • M Beatrix Jones, Committee Member
  • Mark Shriver, Committee Member
  • Jeffrey Arnold Kurland, Committee Chair
Keywords:
  • aromatase
  • Mapmaker Sibs
  • genome screen
  • linkage analysis
  • homosexuality
  • affected sibpair
  • candidate gene
Abstract:
ABSTRACT The causes of differences in sexual orientation are poorly understood. Although behavior genetic analyses have found that homosexuality is familial, candidate gene studies reveal no mechanisms that influence the development of the trait. Previous studies of a region of the X chromosome have shown a statistically significant excess of allele sharing at loci on Xq28 between pairs of homosexual brothers, but the locus explains only a portion of variance in the trait. Thus, there are potentially other loci throughout the genome that could influence the development and expression of sexual orientation. This thesis contains two reports on male homosexuality. The first considers whether differences in the gene encoding the aromatase enzyme (CYP19), a known factor in mammalian neural masculinization, influence sexual orientation in men. Results of the analyses suggest that variation in CYP19 does not wield such influence and likely undermines the candidacy of this pathway of development of male homosexuality. The second report and major portion of the thesis, consists of a full genome scan of a large collection of sibships containing brothers concordant for homosexuality. An allele-sharing linkage methodology is used to analyze the data. In the analyses, sexual orientation is considered both as a dichotomous phenotype as well as a quantitative trait and the Kinsey scales of sexual orientation are used to define the phenotype. The sample population consists of 144 sibships that comprise either two gay brothers (135 sibpairs) or three gay brothers (9 sibtrios). With available parents and heterosexual siblings, a total of 456 individuals are included in the study. The results suggest that several loci could influence this complex trait, although no conclusive evidence for a particular locus is obtained. Among the conclusions of the report is that a new candidate gene on 9q22, 17- •-Hydroxysteroid Dehydrogenase III (HSD17•3), may influence the development of homosexuality in some men. Other analyses justify continued interest in the Xq28 region but also indicate that separate developmental pathways might influence the trait as well. Dissertation Author: Michael G. DuPree Advisors: Jeffrey Kurland Ken Weiss