Genetic epidemiology of visceral leishmaniasis in northeastern Brazil

Peacock, C. S; Collins, A; Shaw, M. - A; Silveira, Fernando Tobias; Costa, J; Coste, C. H; Nascimento, M. D; Siddiqui, R; Shaw, Jeffrey Jon; Blackwell, J. M

Artigo

Genetic epidemiology of visceral leishmaniasis in northeastern Brazil

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-case pedigrees (824 individuals; 138 nuclear families) from a region of northeastern Braz...

ver descrição completa

Autor principal:	Peacock, C. S
Outros Autores:	Collins, A, Shaw, M. - A, Silveira, Fernando Tobias, Costa, J, Coste, C. H, Nascimento, M. D, Siddiqui, R, Shaw, Jeffrey Jon, Blackwell, J. M
Grau:	Artigo
Idioma:	eng
Publicado em:	Wiley 2021
Assuntos:	Leishmaniose Visceral / parasitologia Leishmaniose Visceral / epidemiologia Leishmaniose Visceral / gen?tica Predisposi??o Gen?tica para Doen?a / gen?tica Suscetibilidade a Doen?as
Acesso em linha:	http://patua.iec.gov.br//handle/iec/4367

id	ir-iec-4367
recordtype	dspace
spelling	ir-iec-43672021-07-20T13:06:15Z Genetic epidemiology of visceral leishmaniasis in northeastern Brazil Peacock, C. S Collins, A Shaw, M. - A Silveira, Fernando Tobias Costa, J Coste, C. H Nascimento, M. D Siddiqui, R Shaw, Jeffrey Jon Blackwell, J. M Leishmaniose Visceral / parasitologia Leishmaniose Visceral / epidemiologia Leishmaniose Visceral / gen?tica Predisposi??o Gen?tica para Doen?a / gen?tica Suscetibilidade a Doen?as 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-case pedigrees (824 individuals; 138 nuclear families) from a region of northeastern Brazil endemic for Leishmania chagasi demonstrates a high relative risk ratio (?2S = 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 (P < 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 ?0.002. The general single locus model was strongly favored (P < 0.001) over a recessive single gene model. Using POINTER, polygenic and multifactorial models were clearly rejected (P < 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-locus 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. 2021-07-20T12:32:31Z 2021-07-20T12:32:31Z 2001 Artigo PEACOCK, C. S. et al. Genetic epidemiology of visceral leishmaniasis in northeastern Brazil. Genetic Epidemiology, v, 20,n. 3, p. 383-396, Apr. 2001. 1098-2272 http://patua.iec.gov.br//handle/iec/4367 10.1002/gepi.8 eng Acesso Aberto application/pdf Wiley
institution	Instituto Evandro Chagas (IEC)
collection	PATUA
language	eng
topic	Leishmaniose Visceral / parasitologia Leishmaniose Visceral / epidemiologia Leishmaniose Visceral / gen?tica Predisposi??o Gen?tica para Doen?a / gen?tica Suscetibilidade a Doen?as
spellingShingle	Leishmaniose Visceral / parasitologia Leishmaniose Visceral / epidemiologia Leishmaniose Visceral / gen?tica Predisposi??o Gen?tica para Doen?a / gen?tica Suscetibilidade a Doen?as Peacock, C. S Genetic epidemiology of visceral leishmaniasis in northeastern Brazil
topic_facet	Leishmaniose Visceral / parasitologia Leishmaniose Visceral / epidemiologia Leishmaniose Visceral / gen?tica Predisposi??o Gen?tica para Doen?a / gen?tica Suscetibilidade a Doen?as
description	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-case pedigrees (824 individuals; 138 nuclear families) from a region of northeastern Brazil endemic for Leishmania chagasi demonstrates a high relative risk ratio (?2S = 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 (P < 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 ?0.002. The general single locus model was strongly favored (P < 0.001) over a recessive single gene model. Using POINTER, polygenic and multifactorial models were clearly rejected (P < 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-locus 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.
format	Artigo
author	Peacock, C. S
author2	Collins, A Shaw, M. - A Silveira, Fernando Tobias Costa, J Coste, C. H Nascimento, M. D Siddiqui, R Shaw, Jeffrey Jon Blackwell, J. M
author2Str	Collins, A Shaw, M. - A Silveira, Fernando Tobias Costa, J Coste, C. H Nascimento, M. D Siddiqui, R Shaw, Jeffrey Jon Blackwell, J. M
title	Genetic epidemiology of visceral leishmaniasis in northeastern Brazil
title_short	Genetic epidemiology of visceral leishmaniasis in northeastern Brazil
title_full	Genetic epidemiology of visceral leishmaniasis in northeastern Brazil
title_fullStr	Genetic epidemiology of visceral leishmaniasis in northeastern Brazil
title_full_unstemmed	Genetic epidemiology of visceral leishmaniasis in northeastern Brazil
title_sort	genetic epidemiology of visceral leishmaniasis in northeastern brazil
publisher	Wiley
publishDate	2021
url	http://patua.iec.gov.br//handle/iec/4367
_version_	1717584520582004736
score	11.755432

Genetic epidemiology of visceral leishmaniasis in northeastern Brazil

Registros relacionados