Population differences of chromosome 22q11.2 duplication structure predispose differentially to microdeletion and inversion.
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| Format: | Artículo científico |
| Language: | en |
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Nature communications
2026
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| author | Porubsky, David Yoo, DongAhn Koundinya, Nidhi Souche, Erika Dishuck, Philip C Dierckxsens, Nicolas Harvey, William T Munson, Katherine M Hoekzema, Kendra Chan, Daniel D Leung, Tiffany Y Santos, Marta S Meynants, Senne Swillen, Ann Breckpot, Jeroen Tsapalou, Vasiliki Hasenfeld, Patrick Korbel, Jan O Lansdorp, Peter M Vermeesch, Joris R Eichler, Evan E |
| author_facet | Porubsky, David Yoo, DongAhn Koundinya, Nidhi Souche, Erika Dishuck, Philip C Dierckxsens, Nicolas Harvey, William T Munson, Katherine M Hoekzema, Kendra Chan, Daniel D Leung, Tiffany Y Santos, Marta S Meynants, Senne Swillen, Ann Breckpot, Jeroen Tsapalou, Vasiliki Hasenfeld, Patrick Korbel, Jan O Lansdorp, Peter M Vermeesch, Joris R Eichler, Evan E Porubsky, David Yoo, DongAhn Koundinya, Nidhi Souche, Erika Dishuck, Philip C Dierckxsens, Nicolas Harvey, William T Munson, Katherine M Hoekzema, Kendra Chan, Daniel D Leung, Tiffany Y Santos, Marta S Meynants, Senne Swillen, Ann Breckpot, Jeroen Tsapalou, Vasiliki Hasenfeld, Patrick Korbel, Jan O Lansdorp, Peter M Vermeesch, Joris R Eichler, Evan E |
| collection | PubMed - marine biology |
| contents | Population differences of chromosome 22q11.2 duplication structure predispose differentially to microdeletion and inversion. Porubsky, David Yoo, DongAhn Koundinya, Nidhi Souche, Erika Dishuck, Philip C Dierckxsens, Nicolas Harvey, William T Munson, Katherine M Hoekzema, Kendra Chan, Daniel D Leung, Tiffany Y Santos, Marta S Meynants, Senne Swillen, Ann Breckpot, Jeroen Tsapalou, Vasiliki Hasenfeld, Patrick Korbel, Jan O Lansdorp, Peter M Vermeesch, Joris R Eichler, Evan E Humans Chromosome Inversion Chromosomes, Human, Pair 22 Haplotypes DiGeorge Syndrome Chromosome Deletion Male Female Genetic Predisposition to Disease Segmental Duplications, Genomic Chromosome Duplication Chromosome 22q11.2 microdeletion syndrome (22q11.2DS) is mediated by high-identity polymorphic low-copy repeats (LCRA-to-D) that have been challenging to sequence characterize. We sequence-resolved 135 chromosome 22q11.2 haplotypes from diverse humans and define 63 distinct structural configurations differing in size by 11-fold for LCRA. This diversity is driven by a 105 kbp segmental duplication flanked by 25 kbp inverted repeats that arose in the apes but expanded in humans ~1 million years ago. African LCRA haplotypes are significantly longer (p = 0.0047) and predicted to be more protective against 22q11.2DS (p = 1.14×10) due to enrichment of inverted 105 kbp repeats. We identify nine distinct (including five recurrent) inversions spanning LCRA-D. Sequencing four families indicates LCRA-D deletions map to 105 kbp repeats, whereas inversions map to the 25 kbp repeats. Here, we show specific haplotype LCR architectures and recurrent large-scale inversions modulate susceptibility to 22q11.2DS and help explain its reduced prevalence among individuals of African ancestry. |
| format | Artículo científico |
| id | pubmed_42000714 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Nature communications |
| record_format | pubmed |
| spellingShingle | Population differences of chromosome 22q11.2 duplication structure predispose differentially to microdeletion and inversion. Porubsky, David Yoo, DongAhn Koundinya, Nidhi Souche, Erika Dishuck, Philip C Dierckxsens, Nicolas Harvey, William T Munson, Katherine M Hoekzema, Kendra Chan, Daniel D Leung, Tiffany Y Santos, Marta S Meynants, Senne Swillen, Ann Breckpot, Jeroen Tsapalou, Vasiliki Hasenfeld, Patrick Korbel, Jan O Lansdorp, Peter M Vermeesch, Joris R Eichler, Evan E Humans Chromosome Inversion Chromosomes, Human, Pair 22 Haplotypes DiGeorge Syndrome Chromosome Deletion Male Female Genetic Predisposition to Disease Segmental Duplications, Genomic Chromosome Duplication Population differences of chromosome 22q11.2 duplication structure predispose differentially to microdeletion and inversion. Porubsky, David Yoo, DongAhn Koundinya, Nidhi Souche, Erika Dishuck, Philip C Dierckxsens, Nicolas Harvey, William T Munson, Katherine M Hoekzema, Kendra Chan, Daniel D Leung, Tiffany Y Santos, Marta S Meynants, Senne Swillen, Ann Breckpot, Jeroen Tsapalou, Vasiliki Hasenfeld, Patrick Korbel, Jan O Lansdorp, Peter M Vermeesch, Joris R Eichler, Evan E Humans Chromosome Inversion Chromosomes, Human, Pair 22 Haplotypes DiGeorge Syndrome Chromosome Deletion Male Female Genetic Predisposition to Disease Segmental Duplications, Genomic Chromosome Duplication Chromosome 22q11.2 microdeletion syndrome (22q11.2DS) is mediated by high-identity polymorphic low-copy repeats (LCRA-to-D) that have been challenging to sequence characterize. We sequence-resolved 135 chromosome 22q11.2 haplotypes from diverse humans and define 63 distinct structural configurations differing in size by 11-fold for LCRA. This diversity is driven by a 105 kbp segmental duplication flanked by 25 kbp inverted repeats that arose in the apes but expanded in humans ~1 million years ago. African LCRA haplotypes are significantly longer (p = 0.0047) and predicted to be more protective against 22q11.2DS (p = 1.14×10) due to enrichment of inverted 105 kbp repeats. We identify nine distinct (including five recurrent) inversions spanning LCRA-D. Sequencing four families indicates LCRA-D deletions map to 105 kbp repeats, whereas inversions map to the 25 kbp repeats. Here, we show specific haplotype LCR architectures and recurrent large-scale inversions modulate susceptibility to 22q11.2DS and help explain its reduced prevalence among individuals of African ancestry. |
| title | Population differences of chromosome 22q11.2 duplication structure predispose differentially to microdeletion and inversion. |
| topic | Humans Chromosome Inversion Chromosomes, Human, Pair 22 Haplotypes DiGeorge Syndrome Chromosome Deletion Male Female Genetic Predisposition to Disease Segmental Duplications, Genomic Chromosome Duplication |
| url | https://pubmed.ncbi.nlm.nih.gov/42000714/ |