Using Balanced Translocation to Discover Novel Disease Causing Genes: Potential Involvement of Basonuclin 2 in Congenital Heart Disease and Palmitoylated Membrane Protein 7 in Maturity-Onset Diabetes of the Young

Show full item record

Title: Using Balanced Translocation to Discover Novel Disease Causing Genes: Potential Involvement of Basonuclin 2 in Congenital Heart Disease and Palmitoylated Membrane Protein 7 in Maturity-Onset Diabetes of the Young
Author: Bhoj, Elizabeth Joyce
Abstract: Patients with balanced chromosomal translocations and disease have been used to identify novel disease -causing genes by examining the genes affected by the chromosomal breakpoints . We have identified a man with unexplained maturity -onset diabetes of the young (MODY ) and a balanced translocation (7q22 ;10p12 ) , and a man carrying a balanced translocation associated with partial anomalous pulmonary venous return (PAPVR ) and hypospadias . / In our first proband , the translocation breakpoints were mapped to high resolution using FISH and somatic cell hybrids and the junctions amplified by PCR and sequenced . No annotated genes were disrupted by the translocation . Three of the four genes bordering the translocation breakpoints showed biallelic transcription in lymphoblastoid cells ; the other gene did not have any informative SNPs . The 10p12 breakpoint was 220 kb 5’ to the Membrane Protein , Palmitoylated (MPP7 ) gene , which encodes a protein required for proper cell polarity . As this biological function is shared by HNF4A , a known MODY gene , the translocation may cause islet cell dysfunction by altering MPP7 expression in a tissue - or a cell -specific fashion . / In our second proband , tiling array comparative genomic hybridization (aCGH ) for chromosomes 9 and 13 was performed on DNA from cultured cells from the productions of conception of his offspring with karyotype (46 ,XX ,der (9 )t (9 ;13 ) (p22 ;q22 ) . The results mapped both breakpoints to kilobase resolution . The chromosome 13 breakpoint lies in an intergenic region . The nearest gene , Lim -domain Only 7 (LMO7 ) , is ~400 kb away . The chromosome 9 breakpoint lies within an intron of basonuclin 2 (BNC2 ) , a gene of unknown function with a complex pattern of alternative transcripts . Expression of LMO7 and BNC2 is enriched in fetal heart and penis . Transcripts from both alleles of LMO7 and BNC2 were present in immortalized lymphocytes with the balanced translocation . One BNC2 missense mutation of unclear significance was identified among 10 patients with sporadic total or PAPVR .
URI: http : / /hdl .handle .net /2152 .5 /243
Date: 2010-05-14

Citation

Using Balanced Translocation to Discover Novel Disease Causing Genes: Potential Involvement of Basonuclin 2 in Congenital Heart Disease and Palmitoylated Membrane Protein 7 in Maturity-Onset Diabetes of the Young. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /243 .

Files in this item

Files Size Format View
bhojelizabeth.pdf 1.086Mb application/pdf View/Open

This item appears in the following Collection(s)

Show full item record

Search DSpace

Advanced Search

Browse