OBJECTIVE: Identification of the breakpoints of disease-associated chromosome rearrangements can provide informative clues to a positional cloning approach for genes responsible for inherited diseases. Recently, we found a three-generation Japanese family segregating balanced chromosome translocation t(9;17)(q32;q12). One of the subjects had cleft lip and palate. We examined whether regions near the breakpoint could be associated with cleft lip and/or palate. METHODS: We determined the breakpoints involved in the translocation by fluorescence in situ hybridization analysis and subsequent long-range polymerase chain reaction. In order to study the role of these disrupted regions in nonsyndromic cleft lip and/or palate, we performed mutation analysis and a haplotype-based transmission disequilibrium test using tagging single-nucleotide polymorphisms in the flanking regions of the breakpoints in white and Filipino nonsyndromic cleft lip and/or palate populations. RESULTS: Sequence analysis demonstrated that two genes, SLC31A1 (solute carrier family 31 member 1) on chromosome 9 and CCL2 (chemokine ligand 2) on chromosome 17, were rearranged with the breaks occurring within their introns. It is interesting that SLC31A1 lies closed to BSPRY (B-box and SPRY domain), which is a candidate for involvement with cleft lip and/or palate. Some of the variants in BSPRY and CCL2 showed significant p values in the cleft lip and/or palate population compared with the control population. There was also statistically significant evidence of transmission distortion for haplotypes on both chromosomes 9 and 17. CONCLUSIONS: The data support previous reports that genes on chromosomal regions of 9q and 17q play an important role in facial development.
OBJECTIVE: Identification of the breakpoints of disease-associated chromosome rearrangements can provide informative clues to a positional cloning approach for genes responsible for inherited diseases. Recently, we found a three-generation Japanese family segregating balanced chromosome translocation t(9;17)(q32;q12). One of the subjects had cleft lip and palate. We examined whether regions near the breakpoint could be associated with cleft lip and/or palate. METHODS: We determined the breakpoints involved in the translocation by fluorescence in situ hybridization analysis and subsequent long-range polymerase chain reaction. In order to study the role of these disrupted regions in nonsyndromic cleft lip and/or palate, we performed mutation analysis and a haplotype-based transmission disequilibrium test using tagging single-nucleotide polymorphisms in the flanking regions of the breakpoints in white and Filipino nonsyndromic cleft lip and/or palate populations. RESULTS: Sequence analysis demonstrated that two genes, SLC31A1 (solute carrier family 31 member 1) on chromosome 9 and CCL2 (chemokine ligand 2) on chromosome 17, were rearranged with the breaks occurring within their introns. It is interesting that SLC31A1 lies closed to BSPRY (B-box and SPRY domain), which is a candidate for involvement with cleft lip and/or palate. Some of the variants in BSPRY and CCL2 showed significant p values in the cleft lip and/or palate population compared with the control population. There was also statistically significant evidence of transmission distortion for haplotypes on both chromosomes 9 and 17. CONCLUSIONS: The data support previous reports that genes on chromosomal regions of 9q and 17q play an important role in facial development.
Authors: H van Bokhoven; J Celli; H Kayserili; E van Beusekom; S Balci; W Brussel; F Skovby; B Kerr; E F Percin; N Akarsu; H G Brunner Journal: Nat Genet Date: 2000-08 Impact factor: 38.330
Authors: Laura A Lettice; Simon J H Heaney; Lorna A Purdie; Li Li; Philippe de Beer; Ben A Oostra; Debbie Goode; Greg Elgar; Robert E Hill; Esther de Graaff Journal: Hum Mol Genet Date: 2003-07-15 Impact factor: 6.150
Authors: P A Jezewski; A R Vieira; C Nishimura; B Ludwig; M Johnson; S E O'Brien; S Daack-Hirsch; R E Schultz; A Weber; B Nepomucena; P A Romitti; K Christensen; I M Orioli; E E Castilla; J Machida; N Natsume; J C Murray Journal: J Med Genet Date: 2003-06 Impact factor: 6.318