Human balanced translocation and mouse gene inactivation implicate Basonuclin 2 in distal urethral development

Elizabeth J. Bhoj, Purita Ramos, Linda A. Baker, Nicholas Cost, Agneta Nordenskjöld, Frederick F. Elder, Steven B. Bleyl, Neil E. Bowles, Cammon B. Arrington, Brigitte Delhomme, Amandine Vanhoutteghem, Philippe Djian, Andrew R. Zinn

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We studied a man with distal hypospadias, partial anomalous pulmonary venous return, mild limb-length inequality and a balanced translocation involving chromosomes 9 and 13. To gain insight into the etiology of his birth defects, we mapped the translocation breakpoints by high-resolution comparative genomic hybridization (CGH), using chromosome 9- and 13-specific tiling arrays to analyze genetic material from a spontaneously aborted fetus with unbalanced segregation of the translocation.The chromosome 13 breakpoint was ̃400 kb away from the nearest gene, but the chromosome 9 breakpoint fell within an intron of Basonuclin 2 (BNC2), a gene that encodes an evolutionarily conserved nuclear zinc-finger protein. The BNC2/Bnc2 gene is abundantly expressed in developing mouse and human periurethral tissues. In all, 6 of 48 unrelated subjects with distal hypospadias had nine novel nonsynonymous substitutions in BNC2, five of which were computationally predicted to be deleterious. In comparison, two of 23 controls with normal penile urethra morphology, each had a novel nonsynonymous substitution in BNC2, one of which was predicted to be deleterious. Bnc2-/- mice of both sexes displayed a high frequency of distal urethral defects; heterozygotes showed similar defects with reduced penetrance. The association of BNC2 disruption with distal urethral defects and the gene's expression pattern indicate that it functions in urethral development.

Original languageEnglish (US)
Pages (from-to)540-546
Number of pages7
JournalEuropean Journal of Human Genetics
Volume19
Issue number5
DOIs
StatePublished - May 2011

Fingerprint

Gene Silencing
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 9
Chromosome Breakpoints
Hypospadias
Genes
Scimitar Syndrome
Aborted Fetus
Comparative Genomic Hybridization
Penetrance
Zinc Fingers
Urethra
Heterozygote
Introns
Extremities
Gene Expression
Proteins

Keywords

  • Basonuclin 2
  • Birth defects
  • Hypospadias
  • Urethra

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Human balanced translocation and mouse gene inactivation implicate Basonuclin 2 in distal urethral development. / Bhoj, Elizabeth J.; Ramos, Purita; Baker, Linda A.; Cost, Nicholas; Nordenskjöld, Agneta; Elder, Frederick F.; Bleyl, Steven B.; Bowles, Neil E.; Arrington, Cammon B.; Delhomme, Brigitte; Vanhoutteghem, Amandine; Djian, Philippe; Zinn, Andrew R.

In: European Journal of Human Genetics, Vol. 19, No. 5, 05.2011, p. 540-546.

Research output: Contribution to journalArticle

Bhoj, EJ, Ramos, P, Baker, LA, Cost, N, Nordenskjöld, A, Elder, FF, Bleyl, SB, Bowles, NE, Arrington, CB, Delhomme, B, Vanhoutteghem, A, Djian, P & Zinn, AR 2011, 'Human balanced translocation and mouse gene inactivation implicate Basonuclin 2 in distal urethral development', European Journal of Human Genetics, vol. 19, no. 5, pp. 540-546. https://doi.org/10.1038/ejhg.2010.245
Bhoj, Elizabeth J. ; Ramos, Purita ; Baker, Linda A. ; Cost, Nicholas ; Nordenskjöld, Agneta ; Elder, Frederick F. ; Bleyl, Steven B. ; Bowles, Neil E. ; Arrington, Cammon B. ; Delhomme, Brigitte ; Vanhoutteghem, Amandine ; Djian, Philippe ; Zinn, Andrew R. / Human balanced translocation and mouse gene inactivation implicate Basonuclin 2 in distal urethral development. In: European Journal of Human Genetics. 2011 ; Vol. 19, No. 5. pp. 540-546.
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