Y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in Sudan
Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishmania donovani is under genetic control. A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan usin...
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| creator | Miller, E Nancy Fadl, Manal Mohamed, Hiba S Elzein, Abier Jamieson, Sarra E Cordell, Heather J Peacock, Christopher S Fakiola, Michaela Raju, Madhuri Khalil, Eltahir A Elhassan, Ahmed Musa, Ahmed M Ibrahim, Muntaser E Blackwell, Jenefer M |
| description | Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishmania donovani is under genetic control. A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related Masalit ethnic group. A primary ten-centimorgan scan followed by refined mapping provided evidence for major loci at 1p22 (LOD score 5.65; nominal p = 1.72 x 10(-7); empirical p < 1 x 10(-5); lambdaS = 5.1) and 6q27 (LOD score 3.74; nominal p = 1.68 x 10(-5); empirical p < 1 x 10(-4); lambdaS = 2.3) that were Y chromosome-lineage and village-specific. Neither village supported a visceral leishmaniasis susceptibility gene on 22q12. The results suggest strong lineage-specific genes due to founder effect and consanguinity in these recently immigrant populations. These chance events in ethnically uniform African populations provide a powerful resource in the search for genes and mechanisms that regulate this complex disease. |
| doi_str_mv | 10.1371/journal.pgen.0030071 |
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A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related Masalit ethnic group. A primary ten-centimorgan scan followed by refined mapping provided evidence for major loci at 1p22 (LOD score 5.65; nominal p = 1.72 x 10(-7); empirical p < 1 x 10(-5); lambdaS = 5.1) and 6q27 (LOD score 3.74; nominal p = 1.68 x 10(-5); empirical p < 1 x 10(-4); lambdaS = 2.3) that were Y chromosome-lineage and village-specific. Neither village supported a visceral leishmaniasis susceptibility gene on 22q12. The results suggest strong lineage-specific genes due to founder effect and consanguinity in these recently immigrant populations. These chance events in ethnically uniform African populations provide a powerful resource in the search for genes and mechanisms that regulate this complex disease.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.0030071</identifier><identifier>PMID: 17500593</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Alleles ; Child ; Child, Preschool ; Chromosome Mapping ; Chromosomes ; Chromosomes, Human, Pair 1 - genetics ; Chromosomes, Human, Pair 6 - genetics ; Chromosomes, Human, Y - genetics ; Consanguinity ; Control ; DNA, Mitochondrial - genetics ; Female ; Genes ; Genetic aspects ; Genetics ; Genetics and Genomics ; Genome, Human - genetics ; Genomics ; Haplotypes ; Health aspects ; Homo (Human) ; Humans ; Kala-azar ; Leishmaniasis, Visceral - genetics ; Lod Score ; Male ; Microsatellite Repeats - genetics ; Molecular Sequence Data ; Parasitic diseases ; Pedigree ; Rural Health ; Rural Population ; Social aspects ; Species Specificity ; Sudan ; Y chromosome</subject><ispartof>PLoS genetics, 2007-05, Vol.3 (5), p.e71-e71</ispartof><rights>COPYRIGHT 2007 Public Library of Science</rights><rights>2007 Miller et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Miller EN, Fadl M, Mohamed HS, Elzein A, Jamieson SE, et al. (2007) Y Chromosome Lineage- and Village-Specific Genes on Chromosomes 1p22 and 6q27 Control Visceral Leishmaniasis in Sudan. PLoS Genet 3(5): e71. doi:10.1371/journal.pgen.0030071</rights><rights>2007 Miller et al. 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c729t-5f169af5f5310b887b2307ca53b4c7d4897259a3c1a056de68b7031d8806f5b63</citedby><cites>FETCH-LOGICAL-c729t-5f169af5f5310b887b2307ca53b4c7d4897259a3c1a056de68b7031d8806f5b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866354/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866354/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17500593$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miller, E Nancy</creatorcontrib><creatorcontrib>Fadl, Manal</creatorcontrib><creatorcontrib>Mohamed, Hiba S</creatorcontrib><creatorcontrib>Elzein, Abier</creatorcontrib><creatorcontrib>Jamieson, Sarra E</creatorcontrib><creatorcontrib>Cordell, Heather J</creatorcontrib><creatorcontrib>Peacock, Christopher S</creatorcontrib><creatorcontrib>Fakiola, Michaela</creatorcontrib><creatorcontrib>Raju, Madhuri</creatorcontrib><creatorcontrib>Khalil, Eltahir A</creatorcontrib><creatorcontrib>Elhassan, Ahmed</creatorcontrib><creatorcontrib>Musa, Ahmed M</creatorcontrib><creatorcontrib>Ibrahim, Muntaser E</creatorcontrib><creatorcontrib>Blackwell, Jenefer M</creatorcontrib><title>Y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in Sudan</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishmania donovani is under genetic control. A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related Masalit ethnic group. A primary ten-centimorgan scan followed by refined mapping provided evidence for major loci at 1p22 (LOD score 5.65; nominal p = 1.72 x 10(-7); empirical p < 1 x 10(-5); lambdaS = 5.1) and 6q27 (LOD score 3.74; nominal p = 1.68 x 10(-5); empirical p < 1 x 10(-4); lambdaS = 2.3) that were Y chromosome-lineage and village-specific. Neither village supported a visceral leishmaniasis susceptibility gene on 22q12. The results suggest strong lineage-specific genes due to founder effect and consanguinity in these recently immigrant populations. These chance events in ethnically uniform African populations provide a powerful resource in the search for genes and mechanisms that regulate this complex disease.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Alleles</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromosome Mapping</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 1 - genetics</subject><subject>Chromosomes, Human, Pair 6 - genetics</subject><subject>Chromosomes, Human, Y - genetics</subject><subject>Consanguinity</subject><subject>Control</subject><subject>DNA, Mitochondrial - genetics</subject><subject>Female</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Genetics and Genomics</subject><subject>Genome, Human - genetics</subject><subject>Genomics</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Homo (Human)</subject><subject>Humans</subject><subject>Kala-azar</subject><subject>Leishmaniasis, Visceral - genetics</subject><subject>Lod Score</subject><subject>Male</subject><subject>Microsatellite Repeats - genetics</subject><subject>Molecular Sequence Data</subject><subject>Parasitic diseases</subject><subject>Pedigree</subject><subject>Rural Health</subject><subject>Rural Population</subject><subject>Social aspects</subject><subject>Species Specificity</subject><subject>Sudan</subject><subject>Y chromosome</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVk1-L1DAUxYso7rr6DUQLwoIPMyZN0rQvwrL4Z2BxwVXBp3CbJp0MaTKbtIt-e9OZqjPig9KHNunvnJucy82ypxgtMeH41caPwYFdbjvllggRhDi-l51ixsiCU0TvH3yfZI9i3CSIVTV_mJ1gzhBiNTnNxq-5XAff--h7lVvjFHRqkYNr8ztj7bSIWyWNNjJPhVTMvTtQxBxvi2KHl7cFz6V3Q_A2aaNUAWxulYnrHpyBaGJuXH4ztuAeZw802KiezO-z7PPbN58u3y-urt-tLi-uFpIX9bBgGpc1aKYZwaipKt4UBHEJjDRU8pamyxSsBiIxIFa2qqwajghuqwqVmjUlOcue73231kcxJxYFJpjQiqFiIlZ7ovWwEdtgegjfhQcjdhs-dALCYKRVoi6o1m0BmCJNy3QgVOAaYQoMFKqrJnm9nquNTa9aqVIWYI9Mj_84sxadvxO4KkvCaDI4nw2Cvx1VHEQ_5Zja4JQfo-CIMVpwlsAXf4B_v9tyT3WQjm-c9qmqTE-repM6pbRJ-xe4LGkS7eq_PBJM3VTfhg7GGMXq5uN_sB_-nb3-csyeH7BrBXZYR2_HwXgXj0G6B2XwMQalfwWNkZgm5GcmYpoQMU9Ikj07bNJv0TwS5AfRYwn_</recordid><startdate>20070501</startdate><enddate>20070501</enddate><creator>Miller, E Nancy</creator><creator>Fadl, Manal</creator><creator>Mohamed, Hiba S</creator><creator>Elzein, Abier</creator><creator>Jamieson, Sarra E</creator><creator>Cordell, Heather J</creator><creator>Peacock, Christopher S</creator><creator>Fakiola, Michaela</creator><creator>Raju, Madhuri</creator><creator>Khalil, Eltahir A</creator><creator>Elhassan, Ahmed</creator><creator>Musa, Ahmed M</creator><creator>Ibrahim, Muntaser E</creator><creator>Blackwell, Jenefer M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20070501</creationdate><title>Y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in Sudan</title><author>Miller, E Nancy ; Fadl, Manal ; Mohamed, Hiba S ; Elzein, Abier ; Jamieson, Sarra E ; Cordell, Heather J ; Peacock, Christopher S ; Fakiola, Michaela ; Raju, Madhuri ; Khalil, Eltahir A ; Elhassan, Ahmed ; Musa, Ahmed M ; Ibrahim, Muntaser E ; Blackwell, Jenefer M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c729t-5f169af5f5310b887b2307ca53b4c7d4897259a3c1a056de68b7031d8806f5b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Alleles</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chromosome Mapping</topic><topic>Chromosomes</topic><topic>Chromosomes, Human, Pair 1 - genetics</topic><topic>Chromosomes, Human, Pair 6 - genetics</topic><topic>Chromosomes, Human, Y - genetics</topic><topic>Consanguinity</topic><topic>Control</topic><topic>DNA, Mitochondrial - genetics</topic><topic>Female</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetics</topic><topic>Genetics and Genomics</topic><topic>Genome, Human - genetics</topic><topic>Genomics</topic><topic>Haplotypes</topic><topic>Health aspects</topic><topic>Homo (Human)</topic><topic>Humans</topic><topic>Kala-azar</topic><topic>Leishmaniasis, Visceral - genetics</topic><topic>Lod Score</topic><topic>Male</topic><topic>Microsatellite Repeats - genetics</topic><topic>Molecular Sequence Data</topic><topic>Parasitic diseases</topic><topic>Pedigree</topic><topic>Rural Health</topic><topic>Rural Population</topic><topic>Social aspects</topic><topic>Species Specificity</topic><topic>Sudan</topic><topic>Y chromosome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miller, E Nancy</creatorcontrib><creatorcontrib>Fadl, Manal</creatorcontrib><creatorcontrib>Mohamed, Hiba S</creatorcontrib><creatorcontrib>Elzein, Abier</creatorcontrib><creatorcontrib>Jamieson, Sarra E</creatorcontrib><creatorcontrib>Cordell, Heather J</creatorcontrib><creatorcontrib>Peacock, Christopher S</creatorcontrib><creatorcontrib>Fakiola, Michaela</creatorcontrib><creatorcontrib>Raju, Madhuri</creatorcontrib><creatorcontrib>Khalil, Eltahir A</creatorcontrib><creatorcontrib>Elhassan, Ahmed</creatorcontrib><creatorcontrib>Musa, Ahmed M</creatorcontrib><creatorcontrib>Ibrahim, Muntaser E</creatorcontrib><creatorcontrib>Blackwell, Jenefer M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miller, E Nancy</au><au>Fadl, Manal</au><au>Mohamed, Hiba S</au><au>Elzein, Abier</au><au>Jamieson, Sarra E</au><au>Cordell, Heather J</au><au>Peacock, Christopher S</au><au>Fakiola, Michaela</au><au>Raju, Madhuri</au><au>Khalil, Eltahir A</au><au>Elhassan, Ahmed</au><au>Musa, Ahmed M</au><au>Ibrahim, Muntaser E</au><au>Blackwell, Jenefer M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in Sudan</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2007-05-01</date><risdate>2007</risdate><volume>3</volume><issue>5</issue><spage>e71</spage><epage>e71</epage><pages>e71-e71</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishmania donovani is under genetic control. A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related Masalit ethnic group. A primary ten-centimorgan scan followed by refined mapping provided evidence for major loci at 1p22 (LOD score 5.65; nominal p = 1.72 x 10(-7); empirical p < 1 x 10(-5); lambdaS = 5.1) and 6q27 (LOD score 3.74; nominal p = 1.68 x 10(-5); empirical p < 1 x 10(-4); lambdaS = 2.3) that were Y chromosome-lineage and village-specific. Neither village supported a visceral leishmaniasis susceptibility gene on 22q12. The results suggest strong lineage-specific genes due to founder effect and consanguinity in these recently immigrant populations. These chance events in ethnically uniform African populations provide a powerful resource in the search for genes and mechanisms that regulate this complex disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>17500593</pmid><doi>10.1371/journal.pgen.0030071</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Alleles Child Child, Preschool Chromosome Mapping Chromosomes Chromosomes, Human, Pair 1 - genetics Chromosomes, Human, Pair 6 - genetics Chromosomes, Human, Y - genetics Consanguinity Control DNA, Mitochondrial - genetics Female Genes Genetic aspects Genetics Genetics and Genomics Genome, Human - genetics Genomics Haplotypes Health aspects Homo (Human) Humans Kala-azar Leishmaniasis, Visceral - genetics Lod Score Male Microsatellite Repeats - genetics Molecular Sequence Data Parasitic diseases Pedigree Rural Health Rural Population Social aspects Species Specificity Sudan Y chromosome |
| title | Y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in Sudan |
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