A genome‐wide linkage scan for cleft lip and cleft palate identifies a novel locus on 8p11‐23

Riley, Bridget; Schultz, R. E.; Cooper, Margaret E.; Goldstein-McHenry, T.; Daack-Hirsch, Sandra; Lee, K. T.; Dragan, Ecaterina; Vieira, Alexandre R.; Lidral, Andrew C.; Marazita, Mary L.; Murray, Jeffrey C.

doi:10.1002/ajmg.a.31673

Cited by 46 publications

(39 citation statements)

References 49 publications

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“…These signals are near to the 48 cM signal we previously reported [Riley et al, 2007] with a LOD score of 2.38 in 220 Filipino families. Fine mapping work also presented in Riley et al [2007] showed both linkage and association positive results for markers in FGFR1 and BAG4, while either linkage or association showed positive results for markers in SLC18A1, EPHX2, and FZD3. However, under a more strict criteria correcting for multiple testing, none of these results would be statistically significant.…”

Section: Discussionsupporting

confidence: 77%

“…Our preliminary study indicated three regions that yielded suggestive positive linkage results (LOD scores higher than 1.0) in 220 multiplex extended Filipino kindreds: 2p21, 6q23, and 8p21. The highest signal was in 8p11-23 (single point recessive LOD score =1.2 and multipoint recessive LOD score =2.3) and follow up studies with 271 families showed suggestive linkage disequilibrium results for FUT10, BAG4, and FGFR1 [Riley et al, 2007]. Even though this was a large study of 220 families (567 affected and 1,109 unaffected family members genotyped), the results were just modest.…”

Section: Introductionmentioning

confidence: 75%

“…These genotypes were derived at the Center for Inherited Disease Research (CIDR) [Riley et al, 2007]. We performed a genome wide search for suggestive loci linked to clefts with and without dental anomalies outside the cleft area as an extension of the cleft phenotype.…”

Section: Genome Wide Scan Analysismentioning

confidence: 99%

“…For the parametric linkage analysis, allele frequencies were estimated from unaffected founders in the original group of families [Riley et al, 2007]. The genetic model parameters were taken from segregation analysis results in a sample of the Filipino families (unpublished results).…”

Section: Genome Wide Scan Analysismentioning

confidence: 99%

See 3 more Smart Citations

A genome wide linkage scan for cleft lip and palate and dental anomalies

Vieira

McHenry

Daack-Hirsch

et al. 2008

American J of Med Genetics Pt A

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 75%

Section: Genome Wide Scan Analysismentioning

confidence: 99%

Section: Genome Wide Scan Analysismentioning

confidence: 99%

See 2 more Smart Citations

A genome wide linkage scan for cleft lip and palate and dental anomalies

Vieira

McHenry

Daack-Hirsch

et al. 2008

American J of Med Genetics Pt A

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show abstract

“…Egfr, Bmp4, Bmpr1 and Folbp1) (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Eight genome scans have identified regions that may potentially harbor NSCLP susceptibility genes (19)(20)(21)(22)(23)(24)(25). In 2000, Prescott et al (26) identified nine chromosomal regions that are associated with orofacial clefting in their Caucasian NSCLP sib-pair population.…”

Section: Introductionmentioning

confidence: 99%

CRISPLD2: a novel NSCLP candidate gene

Chiquet¹,

Lidral²,

Stal³

et al. 2007

Human Molecular Genetics

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Non-syndromic cleft lip with or without cleft palate (NSCLP) results from the complex interaction between genes and environmental factors. Candidate gene analysis and genome scans have been employed to identify the genes contributing to NSCLP. In this study, we evaluated the 16q24.1 chromosomal region, which has been identified by multiple genome scans as an NSCLP region of interest. Two candidate genes were found in the region: interferon regulatory factor 8 (IRF8) and cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2). Initially, Caucasian and Hispanic NSCLP multiplex families and simplex parent-child trios were genotyped for single nucleotide polymorphisms (SNPs) in both IRF8 and CRISPLD2. CRISPLD2 was subsequently genotyped in a data set comprised of NSCLP families from Colombia, South America. Linkage disequilibrium analysis identified a significant association between CRISPLD2 and NSCLP in both our Caucasian and Hispanic NSCLP cohorts. SNP rs1546124 and haplotypes between rs1546124 and either rs4783099 or rs16974880 were significant in the Caucasian multiplex population (P = 0.01, P = 0.002 and P = 0.001, respectively). An altered transmission of CRISPLD2 SNPs rs8061351 (P = 0.02) and rs2326398 (P = 0.06) was detected in the Hispanic population. No association was found between CRISPLD2 and our Colombian population or IRF8 and NSCLP. In situ hybridization showed that CRISPLD2 is expressed in the mandible, palate and

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Genome‐wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin

Mangold

Reutter

Birnbaum

et al. 2009

American J of Med Genetics Pt A

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Orofacial clefts are among the most common of all congenital disorders. Nonsyndromic cases of cleft lip with or without cleft palate (NSCL/P) and cleft palate only (NSCPO) are considered to have a multifactorial etiology which involves both genetic and environmental factors. We present the results of a genome-wide linkage scan in 91 families of central European descent with nonsyndromic orofacial clefts (NSC). The sample included 74 NSCL/P families, 15 NSCPO families, and 2 mixed families (a total of 217 affected and 230 unaffected individuals were genotyped). We genotyped 542 microsatellite markers (average intermarker distance = 6.9 cM). Multipoint nonparametric linkage analysis was performed using Allegro 2.0f. In addition to the factors investigated in previous genome-wide linkage analyses, we searched for sex-specific susceptibility loci, loci demonstrating parental imprinting and loci that are shared by NSCL/P and NSCPO. Several genomic regions likely to contain susceptibility loci for NSC were identified at the level of nominal significance. Some of these overlap with regions identified in previous studies. Suggestive evidence of linkage was obtained for the loci 4q21-q26 and 1p31-p21, with the chromosome 1 locus showing a male-specific genetic effect. Our study has identified promising chromosomal regions for the identification of NSC-associated genes, and demonstrates the importance of performing detailed statistical analyses which take into account complex genetic mechanisms such as sex-specific effects and genomic imprinting. Further research in large patient samples is necessary to identify factors common to NSCL/P and NSCPO.

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A genome‐wide linkage scan for cleft lip and cleft palate identifies a novel locus on 8p11‐23

Cited by 46 publications

References 49 publications

A genome wide linkage scan for cleft lip and palate and dental anomalies

A genome wide linkage scan for cleft lip and palate and dental anomalies

CRISPLD2: a novel NSCLP candidate gene

Genome‐wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin

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