Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects

Publication Date:
2018-01-05
Publisher:
Genetics Society of America (GSA)
Electronic ISSN:
2160-1836
Topics:
Biology
Published by:
http://www.genetics-gsa.org/
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autor Rambo-Martin, B. L., Mulle, J. G., Cutler, D. J., Bean, L. J. H., Rosser, T. C., Dooley, K. J., Cua, C., Capone, G., Maslen, C. L., Reeves, R. H., Sherman, S. L., Zwick, M. E.
beschreibung One in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: (1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and (2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 198 case individuals with DS+AVSD, and 211 control individuals with DS and a normal heart, using a custom microarray with dense probes tiled on chromosome 21 for array CGH (aCGH). We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. We also showed that previously DS+AVSD (DS and a complete AVSD)-associated common CNVs on chromosome 21 failed to replicate. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population.
citation_standardnr 6130011
datenlieferant ipn_articles
feed_id 169615
feed_publisher Genetics Society of America (GSA)
feed_publisher_url http://www.genetics-gsa.org/
insertion_date 2018-01-05
journaleissn 2160-1836
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher Genetics Society of America (GSA)
quelle G3: Genes, Genomes, Genetics
relation http://www.g3journal.org/cgi/content/short/8/1/105?rss=1
search_space articles
shingle_author_1 Rambo-Martin, B. L., Mulle, J. G., Cutler, D. J., Bean, L. J. H., Rosser, T. C., Dooley, K. J., Cua, C., Capone, G., Maslen, C. L., Reeves, R. H., Sherman, S. L., Zwick, M. E.
shingle_author_2 Rambo-Martin, B. L., Mulle, J. G., Cutler, D. J., Bean, L. J. H., Rosser, T. C., Dooley, K. J., Cua, C., Capone, G., Maslen, C. L., Reeves, R. H., Sherman, S. L., Zwick, M. E.
shingle_author_3 Rambo-Martin, B. L., Mulle, J. G., Cutler, D. J., Bean, L. J. H., Rosser, T. C., Dooley, K. J., Cua, C., Capone, G., Maslen, C. L., Reeves, R. H., Sherman, S. L., Zwick, M. E.
shingle_author_4 Rambo-Martin, B. L., Mulle, J. G., Cutler, D. J., Bean, L. J. H., Rosser, T. C., Dooley, K. J., Cua, C., Capone, G., Maslen, C. L., Reeves, R. H., Sherman, S. L., Zwick, M. E.
shingle_catch_all_1 Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects
One in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: (1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and (2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 198 case individuals with DS+AVSD, and 211 control individuals with DS and a normal heart, using a custom microarray with dense probes tiled on chromosome 21 for array CGH (aCGH). We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. We also showed that previously DS+AVSD (DS and a complete AVSD)-associated common CNVs on chromosome 21 failed to replicate. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population.
Rambo-Martin, B. L., Mulle, J. G., Cutler, D. J., Bean, L. J. H., Rosser, T. C., Dooley, K. J., Cua, C., Capone, G., Maslen, C. L., Reeves, R. H., Sherman, S. L., Zwick, M. E.
Genetics Society of America (GSA)
2160-1836
21601836
shingle_catch_all_2 Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects
One in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: (1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and (2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 198 case individuals with DS+AVSD, and 211 control individuals with DS and a normal heart, using a custom microarray with dense probes tiled on chromosome 21 for array CGH (aCGH). We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. We also showed that previously DS+AVSD (DS and a complete AVSD)-associated common CNVs on chromosome 21 failed to replicate. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population.
Rambo-Martin, B. L., Mulle, J. G., Cutler, D. J., Bean, L. J. H., Rosser, T. C., Dooley, K. J., Cua, C., Capone, G., Maslen, C. L., Reeves, R. H., Sherman, S. L., Zwick, M. E.
Genetics Society of America (GSA)
2160-1836
21601836
shingle_catch_all_3 Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects
One in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: (1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and (2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 198 case individuals with DS+AVSD, and 211 control individuals with DS and a normal heart, using a custom microarray with dense probes tiled on chromosome 21 for array CGH (aCGH). We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. We also showed that previously DS+AVSD (DS and a complete AVSD)-associated common CNVs on chromosome 21 failed to replicate. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population.
Rambo-Martin, B. L., Mulle, J. G., Cutler, D. J., Bean, L. J. H., Rosser, T. C., Dooley, K. J., Cua, C., Capone, G., Maslen, C. L., Reeves, R. H., Sherman, S. L., Zwick, M. E.
Genetics Society of America (GSA)
2160-1836
21601836
shingle_catch_all_4 Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects
One in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: (1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and (2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 198 case individuals with DS+AVSD, and 211 control individuals with DS and a normal heart, using a custom microarray with dense probes tiled on chromosome 21 for array CGH (aCGH). We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. We also showed that previously DS+AVSD (DS and a complete AVSD)-associated common CNVs on chromosome 21 failed to replicate. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population.
Rambo-Martin, B. L., Mulle, J. G., Cutler, D. J., Bean, L. J. H., Rosser, T. C., Dooley, K. J., Cua, C., Capone, G., Maslen, C. L., Reeves, R. H., Sherman, S. L., Zwick, M. E.
Genetics Society of America (GSA)
2160-1836
21601836
shingle_title_1 Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects
shingle_title_2 Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects
shingle_title_3 Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects
shingle_title_4 Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects
timestamp 2025-06-30T23:31:46.217Z
titel Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects
titel_suche Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects
topic W
uid ipn_articles_6130011