AIM: We wished to identify markers associated with allelic nondisjunction in nuclear families with Down syndrome (DS) offspring. Since the GRIK1 and GARS-AIRS-GART genes, mapping to chromosome 21q22.1, may be informative in this regard, we genotyped four single-nucleotide polymorphisms [30952599(A/G) rs363484; 30924733(A/G) rs363506; 34901423(A/G) rs2834235; 34877070(A/G) rs7283354] present in these genes using the SNaPshot(™) assay protocol. RESULTS: We have reported 30952599(A/G)-rs363484 to be monomorphic in our sample population. Genotyping revealed 35/65 families to be informative for 34877070(A/G)-rs7283354 (GARS-AIRS-GART), whereas only 25/65 and 11/65 are informative for 34901423(A/G)-rs2834235 (GARS-AIRS-GART) and 30924733(A/G)-rs363506 (GRIK1) polymorphisms, respectively. The parent- and stage-of-origin of nondisjunction could be traced in 48/65 families using at least one polymorphic marker. A single trio provided internal validation for assignment of the parent- and stage-of-origin of nondisjunction whereby the nondisjoining alleles were independently identified as G-rs363506, G-rs2834235, and G-rs7283354, respectively. An enhanced ratio of meiosis-I to meiosis-II errors during maternal or paternal meioses accounts for allelic nondisjunction. CONCLUSIONS: The SNaPshot assay is quantitative and permits multiplexing for detection of allelic nondisjunction. Inclusion of additional informative chromosome 21-specific markers may aid rapid aneuploidy detection, screening, and prenatal counseling of parents at risk of having babies with DS.
AIM: We wished to identify markers associated with allelic nondisjunction in nuclear families with Down syndrome (DS) offspring. Since the GRIK1 and GARS-AIRS-GART genes, mapping to chromosome 21q22.1, may be informative in this regard, we genotyped four single-nucleotide polymorphisms [30952599(A/G) rs363484; 30924733(A/G) rs363506; 34901423(A/G) rs2834235; 34877070(A/G) rs7283354] present in these genes using the SNaPshot(™) assay protocol. RESULTS: We have reported 30952599(A/G)-rs363484 to be monomorphic in our sample population. Genotyping revealed 35/65 families to be informative for 34877070(A/G)-rs7283354 (GARS-AIRS-GART), whereas only 25/65 and 11/65 are informative for 34901423(A/G)-rs2834235 (GARS-AIRS-GART) and 30924733(A/G)-rs363506 (GRIK1) polymorphisms, respectively. The parent- and stage-of-origin of nondisjunction could be traced in 48/65 families using at least one polymorphic marker. A single trio provided internal validation for assignment of the parent- and stage-of-origin of nondisjunction whereby the nondisjoining alleles were independently identified as G-rs363506, G-rs2834235, and G-rs7283354, respectively. An enhanced ratio of meiosis-I to meiosis-II errors during maternal or paternal meioses accounts for allelic nondisjunction. CONCLUSIONS: The SNaPshot assay is quantitative and permits multiplexing for detection of allelic nondisjunction. Inclusion of additional informative chromosome 21-specific markers may aid rapid aneuploidy detection, screening, and prenatal counseling of parents at risk of having babies with DS.
Authors: Nelson Javier Ramírez; Helen Marcela Belalcázar; Juan José Yunis; Luis Napoleón Quintero; Gonzalo Humberto Arboleda; Humberto Arboleda Journal: Biomedica Date: 2007-05-31 Impact factor: 0.935
Authors: Angelique J A Kooper; Brigitte H W Faas; Ellen Kater-Baats; Ton Feuth; Jasper C J A Janssen; Ineke van der Burgt; Fred K Lotgering; Ad Geurts van Kessel; Arie P T Smits Journal: Prenat Diagn Date: 2008-11 Impact factor: 3.050
Authors: P Gregor; S M Gaston; X Yang; J P O'Regan; D R Rosen; R E Tanzi; D Patterson; J L Haines; H R Horvitz; G R Uhl Journal: Hum Genet Date: 1994-11 Impact factor: 4.132
Authors: K Lindblad-Toh; D M Tanenbaum; M J Daly; E Winchester; W O Lui; A Villapakkam; S E Stanton; C Larsson; T J Hudson; B E Johnson; E S Lander; M Meyerson Journal: Nat Biotechnol Date: 2000-09 Impact factor: 54.908
Authors: Jan O Korbel; Tal Tirosh-Wagner; Alexander Eckehart Urban; Xiao-Ning Chen; Maya Kasowski; Li Dai; Fabian Grubert; Chandra Erdman; Michael C Gao; Ken Lange; Eric M Sobel; Gillian M Barlow; Arthur S Aylsworth; Nancy J Carpenter; Robin Dawn Clark; Monika Y Cohen; Eric Doran; Tzipora Falik-Zaccai; Susan O Lewin; Ira T Lott; Barbara C McGillivray; John B Moeschler; Mark J Pettenati; Siegfried M Pueschel; Kathleen W Rao; Lisa G Shaffer; Mordechai Shohat; Alexander J Van Riper; Dorothy Warburton; Sherman Weissman; Mark B Gerstein; Michael Snyder; Julie R Korenberg Journal: Proc Natl Acad Sci U S A Date: 2009-07-13 Impact factor: 11.205