{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:07:50Z","timestamp":1772118470295,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2001,3,12]],"date-time":"2001-03-12T00:00:00Z","timestamp":984355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2001,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Familial clustering of disease, racial differences in asymptomatic:disease ratios, and studies of mice all point to a genetic component for disease susceptibility in visceral leishmaniasis. Analysis of 87 multi\u2010case pedigrees (824 individuals; 138 nuclear families) from a region of northeastern Brazil endemic for\n                    <jats:italic>Leishmania chagasi<\/jats:italic>\n                    demonstrates a high relative risk ratio (\u03bb\n                    <jats:sub>2S<\/jats:sub>\n                    = 34) to further siblings of affected sibling pairs. Complex segregation analysis using POINTER and COMDS show that all single locus models, as well as polygenic and multifactorial models, provide a signficantly (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001) better fit to the data than a sporadic model. Of the genetic models, the general single locus model was not significantly different from additive or dominant single locus models, all of which gave a gene frequency for the putative disease susceptibility allele of \u223c0.002. The general single locus model was strongly favored (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001) over a recessive single gene model. Using POINTER, polygenic and multifactorial models were clearly rejected (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001 in all cases) in favor of the general single locus model. Using COMDS, the analysis was extended to consider two locus models. Results under a general two\u2010locus model did not differ significantly from the dominant, additive, or general single locus models. Under this model, one locus was estimated at a gene frequency of 0.0017, i.e., in the same range as the disease susceptibility locus for the most favored single gene models, with the second locus at a much lower frequency of 0.0002. Hence, the data support the hypothesis that a single major gene may be important in determining disease susceptibility in this population. To identify the gene(s) involved, a genome scan with replication using two subsets of these larger pedigrees with power to detect linkage is in progress. Genet. Epidemiol. 20:383\u2013396, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/gepi.8","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T17:43:33Z","timestamp":1030297413000},"page":"383-396","source":"Crossref","is-referenced-by-count":42,"title":["Genetic epidemiology of visceral leishmaniasis in northeastern Brazil"],"prefix":"10.1002","volume":"20","author":[{"given":"C.S.","family":"Peacock","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.\u2010A.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Silveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.H.","family":"Coste","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.D.","family":"Nascimento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.J.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.M.","family":"Blackwell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,3,12]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"256","article-title":"Detection of major genes for susceptibility to leprosy and its subtypes in a Caribbean island: Desirade Island","volume":"42","author":"Abel L","year":"1988","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1109\/TAC.1974.1100705"},{"key":"e_1_2_1_4_1","first-page":"203","article-title":"Analise de Custo\u2010efetividade do componente de Leishmaniose no projeto e controle de doencas endemicas no nordeste do Brasil","volume":"2","author":"Akhavan D","year":"1996","journal-title":"Rev Pat Trop"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/514882"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/154.6.1003"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/154.4.639"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1987.tb01598.x"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1093\/infdis\/163.4.853","article-title":"Tumor necrosis factor (cachectin) in human visceral leishmaniasis","volume":"163","author":"Barral\u2010Netto M","year":"1991","journal-title":"J Infect Dis"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182000076678"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/283072a0"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1997.0118"},{"key":"e_1_2_1_13_1","first-page":"7","article-title":"Regulation of Leishmania populations within the host. 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