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DOI: 10.1055/s-2003-41317
Genetics of Endometriosis: A Review of the Positional Cloning Approaches
Publication History
Publication Date:
14 August 2003 (online)
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ABSTRACT
There is increasing evidence that endometriosis is inherited as a complex genetic trait in which multiple genes conferring disease susceptibility interact with each other and the environment to produce the phenotype. Research groups worldwide are trying to identify such susceptibility genes through a “positional cloning” approach. This involves mapping their approximate chromosomal localization using linkage analysis by studying the segregation of DNA markers with disease in families without any knowledge of disease mechanisms. The next stage involves choosing a candidate gene in that region, based upon some theoretical or actual knowledge of disease mechanisms, and showing that polymorphisms in that gene occur more frequently in affected individuals than in controls. The approach should produce a clearer understanding of the molecular and cellular mechanisms involved in disease etiology and pathogenesis. It is unlikely that endometriosis is a single disease entity, and it should be possible to categorize the disease into subtypes on the basis of genetic information. The strategy should lead to the discovery of new drug targets, which will be a major advance given that treatment to date has focused upon crude manipulation of ovarian function.
KEYWORDS
Endometriosis - genetics - positional cloning
REFERENCES
- 1 Jansen R P, Russell P. Nonpigmented endometriosis: clinical, laparoscopic, and pathologic definition. Am J Obstet Gynecol . 1986; 155 1154-1159
- 2 Koninckx P R, Oosterlynck D, D'Hooghe T, Meuleman C. Deeply infiltrating endometriosis is a disease whereas mild endometriosis could be considered a non-disease. Ann N Y Acad Sci . 1994; 734 333-341
- 3 Koninckx P R. Is mild endometriosis a condition occurring intermittently in all women?. Hum Reprod . 1994; 9 2202-2205
- 4 Koninckx P R, Barlow D H, Kennedy S H. Implantation versus infiltration: the Sampson versus the endometriotic disease theory. Gynecol Obstet Invest . 1999; 47 (suppl 1) 3-9
- 5 Kennedy S H, Mardon H, Barlow D H. Familial endometriosis. J Assist Reprod Genet . 1995; 12 32-34
- 6 Stefansson H, Einarsdottir A, Geirsson R T. et al . Endometriosis is not associated with or linked to the GALT gene. Fertil Steril . 2001; 76 5-22
- 7 Hadfield R M, Yudkin P L, Coe C L. et al . Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case-control study. Hum Reprod Update . 1997; 3 109-115
- 8 Stefansson H, Geirsson R T, Steinthorsdottir V. et al . Genetic factors contribute to the risk of developing endometriosis. Hum Reprod . 2002; 17 3-9
- 9 Hadfield R M, Mardon H J, Barlow D H, Kennedy S H. Endometriosis in monozygotic twins. Fertil Steril . 1997; 68 941-942
- 10 Moen M H. Endometriosis in monozygotic twins. Acta Obstet Gynecol Scand . 1994; 73 59-62
- 11 Treloar S A, O'Connor D T, O'Connor V M, Martin N G. Genetic influences on endometriosis in an Australian twin sample. Fertil Steril . 1999; 71 701-710
- 12 Kennedy S H, Hadfield R M, Mardon H, Barlow D H. Age of onset of pain symptoms in non-twin sisters concordant for endometriosis. Hum Reprod . 1996; 11 403-405
- 13 Coxhead D, Thomas E J. Familial inheritance of endometriosis in a British population: a case control study. J Obstet Gynaecol . 1993; 13 42-44
- 14 Kennedy S H, Hadfield R M, Westbrook C. et al . Magnetic resonance imaging to assess familial risk in relatives of women with endometriosis. Lancet . 1998; 352 1440-1441
- 15 Moen M H, Magnus P. The familial risk of endometriosis. Acta Obstet Gynecol Scand . 1993; 72 560-564
- 16 Simpson J L, Elias S, Malinak L R, Buttram Jr C V. Heritable aspects of endometriosis I: genetic studies. Am J Obstet Gynecol . 1980; 137 327-331
- 17 MacKenzie W F, Casey H W. Animal model of human disease: endometriosis. Animal model: endometriosis in rhesus monkeys. Am J Pathol . 1975; 80 341-344
- 18 Zondervan K T, Cardon L R, Desrosiers R. et al . The genetic epidemiology of spontaneous endometriosis in the rhesus monkey. Ann N Y Acad Sci . 2002; 955 233-238
- 19 Kennedy S H. Is there a genetic basis to endometriosis?. Semin Reprod Endocrinol . 1997; 15 309-318
- 20 Koninckx P R, Braet P, Kennedy S H, Barlow D H. Dioxin pollution and endometriosis in Belgium. Hum Reprod . 1994; 9 1001-1002
- 21 Zondervan K T, Cardon L R, Kennedy S H. The genetic basis of endometriosis. Curr Opin Obstet Gynecol . 2001; 13 309-314
- 22 Zondervan K T, Cardon L R, Kennedy S H. Development of a web site for the genetic epidemiology of endometriosis. Fertil Steril . 2002; 78 777-781
- 23 Zondervan K T, Cardon L R, Kennedy S H. What makes a good case-control study?. <~>Design issues for complex genetic traits such as endometriosis. Hum Reprod . 2002; 17 1415-1423
- 24 Weeks D E, Lange K. The affected-pedigree-member method of linkage analysis. Am J Hum Genet . 1988; 42 315-326
- 25 Kruglyak L, Lander E S. High-resolution genetic mapping of complex traits. Am J Hum Genet . 1995; 56 5-23
- 26 Kruglyak L, Lander E S. Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet . 1995; 57 2-54
- 27 Lander E, Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet . 1995; 11 3-7
- 28 Davies J L, Kawaguchi Y, Bennett S T. et al . A genome-wide search for human type 1 diabetes susceptibility genes. Nature . 1994; 371 130-136
- 29 Sandford A J, Shirakawa T, Moffatt M F. et al . Localisation of atopy and beta subunit of high-affinity IgE receptor (Fc epsilon RI) on chromosome 11q. Lancet . 1993; 341 332-334
- 30 Satsangi J, Parkes M, Louis E. et al . Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat Genet . 1996; 14 199-202
- 31 Cramer D W, Hornstein M D, Ng W G, Barbieri R L. Endometriosis associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT). Mol Hum Reprod . 1996; 2 149-152
- 32 Hadfield R M, Manek S, Nakago S. et al . Absence of a relationship between endometriosis and the N314D polymorphism of galactose-1-phosphate uridyl transferase in a UK population. Mol Hum Reprod . 1999; 5 990-993
- 33 Morland S J, Jiang X, Hitchcock A, Thomas E J, Campbell I G. Mutation of galactose-1-phosphate uridyl transferase and its association with ovarian cancer and endometriosis. Int J Cancer . 1998; 77 825-827
- 34 Hull D B, Gibson C, Hart A. et al . The heritability of endometriosis in large Utah families. Fertil Steril . 2002; 77 S21
- 35 Treloar S A, Hadfield R M, Montgomery G. et al . The International Endogene Study: a collection of families for genetic research in endometriosis. Fertil Steril . 2002; 78 679-685
- 36 O'Connor D T. Endometriosis. In: Singer A, ed. Current Reviews in Obstetrics and Gynaecology Edinburgh: Churchill Livingstone; 1987
- 37 Treloar S A, Do K A, O'Connor V M. et al . Predictors of hysterectomy: an Australian study. Am J Obstet Gynecol . 1999; 180 945-954
- 38 Kennedy S H, Bennett S, Weeks D E. Affected sib-pair analysis in endometriosis. Hum Reprod Update . 2001; 7 411-418
- 39 Treloar S A, Bahlo M, Ewen K. et al . Suggestive linkage for endometriosis found in genome-wide scan. Am J Hum Genet . 2000; 67 (suppl 2) 318