Chromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease.
Hirschsprung disease (HSCR) genetics is a paradigm for the study and understanding of multigenic disorders. Association between Down syndrome and HSCR suggests that genetic factors that predispose to HSCR map to chromosome 21. To identify these additional factors, we performed a dose-dependent assoc...
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oai:doaj.org-article:be655f622d9a471dba04553323858f202021-11-18T07:46:49ZChromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease.1932-620310.1371/journal.pone.0062519https://doaj.org/article/be655f622d9a471dba04553323858f202013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23671607/?tool=EBIhttps://doaj.org/toc/1932-6203Hirschsprung disease (HSCR) genetics is a paradigm for the study and understanding of multigenic disorders. Association between Down syndrome and HSCR suggests that genetic factors that predispose to HSCR map to chromosome 21. To identify these additional factors, we performed a dose-dependent association study on chromosome 21 in Down syndrome patients with HSCR. Assessing 10,895 SNPs in 26 Caucasian cases and their parents led to identify two associated SNPs (rs2837770 and rs8134673) at chromosome-wide level. Those SNPs, which were located in intron 3 of the DSCAM gene within a 19 kb-linkage disequilibrium block region were in complete association and are consistent with DSCAM expression during enteric nervous system development. We replicated the association of HSCR with this region in an independent sample of 220 non-syndromic HSCR Caucasian patients and their parents. At last, we provide the functional rationale to the involvement of DSCAM by network analysis and assessment of SOX10 regulation. Our results reveal the involvement of DSCAM as a HSCR susceptibility locus, both in Down syndrome and HSCR isolated cases. This study further ascertains the chromosome-scan dose-dependent methodology used herein as a mean to map the genetic bases of other sub-phenotypes both in Down syndrome and other aneuploidies.Anne-Sophie JannotAnna PeletAlexandra Henrion-CaudeAsma ChaouiMarine Masse-MorelStacey ArnoldDamien SanlavilleIsabella CeccheriniSalud BorregoRobert M W HofstraArnold MunnichNadège BondurandAravinda ChakravartiFrançoise Clerget-DarpouxJeanne AmielStanislas LyonnetPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e62519 (2013) |
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Medicine R Science Q Anne-Sophie Jannot Anna Pelet Alexandra Henrion-Caude Asma Chaoui Marine Masse-Morel Stacey Arnold Damien Sanlaville Isabella Ceccherini Salud Borrego Robert M W Hofstra Arnold Munnich Nadège Bondurand Aravinda Chakravarti Françoise Clerget-Darpoux Jeanne Amiel Stanislas Lyonnet Chromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease. |
| description |
Hirschsprung disease (HSCR) genetics is a paradigm for the study and understanding of multigenic disorders. Association between Down syndrome and HSCR suggests that genetic factors that predispose to HSCR map to chromosome 21. To identify these additional factors, we performed a dose-dependent association study on chromosome 21 in Down syndrome patients with HSCR. Assessing 10,895 SNPs in 26 Caucasian cases and their parents led to identify two associated SNPs (rs2837770 and rs8134673) at chromosome-wide level. Those SNPs, which were located in intron 3 of the DSCAM gene within a 19 kb-linkage disequilibrium block region were in complete association and are consistent with DSCAM expression during enteric nervous system development. We replicated the association of HSCR with this region in an independent sample of 220 non-syndromic HSCR Caucasian patients and their parents. At last, we provide the functional rationale to the involvement of DSCAM by network analysis and assessment of SOX10 regulation. Our results reveal the involvement of DSCAM as a HSCR susceptibility locus, both in Down syndrome and HSCR isolated cases. This study further ascertains the chromosome-scan dose-dependent methodology used herein as a mean to map the genetic bases of other sub-phenotypes both in Down syndrome and other aneuploidies. |
| format |
article |
| author |
Anne-Sophie Jannot Anna Pelet Alexandra Henrion-Caude Asma Chaoui Marine Masse-Morel Stacey Arnold Damien Sanlaville Isabella Ceccherini Salud Borrego Robert M W Hofstra Arnold Munnich Nadège Bondurand Aravinda Chakravarti Françoise Clerget-Darpoux Jeanne Amiel Stanislas Lyonnet |
| author_facet |
Anne-Sophie Jannot Anna Pelet Alexandra Henrion-Caude Asma Chaoui Marine Masse-Morel Stacey Arnold Damien Sanlaville Isabella Ceccherini Salud Borrego Robert M W Hofstra Arnold Munnich Nadège Bondurand Aravinda Chakravarti Françoise Clerget-Darpoux Jeanne Amiel Stanislas Lyonnet |
| author_sort |
Anne-Sophie Jannot |
| title |
Chromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease. |
| title_short |
Chromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease. |
| title_full |
Chromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease. |
| title_fullStr |
Chromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease. |
| title_full_unstemmed |
Chromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease. |
| title_sort |
chromosome 21 scan in down syndrome reveals dscam as a predisposing locus in hirschsprung disease. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/be655f622d9a471dba04553323858f20 |
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