Journal of Down Syndrome & chromosome abnormalities最新文献

筛选

英文中文

Variation in the Zinc Finger of PRDM9 is Associated with the Absence of Recombination along Nondisjoined Chromosomes 21 of Maternal Origin. PRDM9锌指的变异与母源21非连接染色体重组的缺失有关

Journal of Down Syndrome & chromosome abnormalities Pub Date : 2016-12-01 Epub Date: 2016-11-23 DOI: 10.4172/2472-1115.1000115

Tiffany Renee Oliver, Candace Middlebrooks, Ariel Harden, Nyeisha Scott, Blair Johnson, Jillian Jones, Christin Walker, Corinthia Wilkerson, Sha-Hanna Saffold, Abisola Akinseye, Tunde Smith, Eleanor Feingold, Stephanie L Sherman

{"title":"Variation in the Zinc Finger of PRDM9 is Associated with the Absence of Recombination along Nondisjoined Chromosomes 21 of Maternal Origin.","authors":"Tiffany Renee Oliver, Candace Middlebrooks, Ariel Harden, Nyeisha Scott, Blair Johnson, Jillian Jones, Christin Walker, Corinthia Wilkerson, Sha-Hanna Saffold, Abisola Akinseye, Tunde Smith, Eleanor Feingold, Stephanie L Sherman","doi":"10.4172/2472-1115.1000115","DOIUrl":"10.4172/2472-1115.1000115","url":null,"abstract":"Variation in the zinc finger-binding domain (ZFBD) of the protein PR Domain-Containing Protein 9 (PRDM9) is associated with altered placement of recombination in the human genome. As both the absence and altered placement of recombination are observed among chromosomes 21 that nondisjoin, we genotyped the PRDM9 ZFBD among mothers of children with Trisomy 21 in efforts to determine if variation within this region is associated with the recombination-related risk for chromosome 21 nondisjunction (NDJ). In our approach, PCR was used to amplify the ZFBD of PRDM9 and products were then subjected to bi-directional Sanger sequencing. DNA sequencing reads were aligned and compared to the sequence of the PRDM9 alleles previously identified. Chi-Square analysis was used to compare allele frequencies between cases (N=235, mothers of children with maternally-derived Trisomy 21) and controls (N=48, fathers of children with maternally-derived Trisomy 21). Results of our analysis showed that the frequency of PRDM9 ZF minor alleles is significantly increased among women displaying NDJ of chromosome 21 and no recombination on 21q (p=0.02). Even more, when compared to those for the PRDM9 major A-allele, these minor alleles displayed fewer predicted binding sites on 21q. These findings suggest that allelic variation in the ZF of PRDM9 may play a role in the risk for chromosome 21 NDJ by leading to reduced recombination on 21q.","PeriodicalId":73711,"journal":{"name":"Journal of Down Syndrome & chromosome abnormalities","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10310745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Beyond Trisomy 21: Phenotypic Variability in People with Down Syndrome Explained by Further Chromosome Mis-segregation and Mosaic Aneuploidy. 21三体以外:唐氏综合症患者的表型变异由进一步的染色体错分离和马赛克非整倍体解释。

Journal of Down Syndrome & chromosome abnormalities Pub Date : 2016-01-01 Epub Date: 2016-03-31 DOI: 10.4172/2472-1115.1000109

Huntington Potter

{"title":"Beyond Trisomy 21: Phenotypic Variability in People with Down Syndrome Explained by Further Chromosome Mis-segregation and Mosaic Aneuploidy.","authors":"Huntington Potter","doi":"10.4172/2472-1115.1000109","DOIUrl":"https://doi.org/10.4172/2472-1115.1000109","url":null,"abstract":"Phenotypic variability is a fundamental feature of the human population and is particularly evident among people with Down syndrome and/or Alzheimer's disease. Herein, we review current theories of the potential origins of this phenotypic variability and propose a novel mechanism based on our finding that the Alzheimer's disease-associated Aβ peptide, encoded on chromosome 21, disrupts the mitotic spindle, induces abnormal chromosome segregation, and produces mosaic populations of aneuploid cells in all tissues of people with Alzheimer's disease and in mouse and cell models thereof. Thus, individuals exposed to increased levels of the Aβ peptide should accumulate mosaic populations of aneuploid cells, with different chromosomes affected in different tissues and in different individuals. Specifically, people with Down syndrome, who express elevated levels of Aβ peptide throughout their lifetimes, would be predicted to accumulate additional types of aneuploidy, beyond trisomy 21 and including changes in their trisomy 21 status, in mosaic cell populations. Such mosaic aneuploidy would introduce a novel form of genetic variability that could potentially underlie much of the observed phenotypic variability among people with Down syndrome, and possibly also among people with Alzheimer's disease. This mosaic aneuploidy theory of phenotypic variability in Down syndrome is supported by several observations, makes several testable predictions, and identifies a potential approach to reducing the frequency of some of the most debilitating features of Down syndrome, including Alzheimer's disease.","PeriodicalId":73711,"journal":{"name":"Journal of Down Syndrome & chromosome abnormalities","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2472-1115.1000109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35892959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13