A genome‐wide scan for loci predisposing to non‐syndromic cleft lip with or without cleft palate in two large Syrian families

Wyszynski, Diego F.; Albacha-Hejazi, Hasan; Aldirani, Mohammed; Hammod, Moustafa; Shkair, Hikmat; Karam, Ahmed; Alashkar, Jehad; Holmes, Taura N.; Pugh, Elizabeth; Doheny, Kimberly F.; McIntosh, Iain; Beaty, Terri H.; Bailey-Wilson, Joan E.

doi:10.1002/ajmg.a.20283

Cited by 50 publications

(41 citation statements)

References 78 publications

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“…This region was first identified by Prescott et al in a genome scan of Caucasian NSCLP sib pairs, and subsequently in four other genome scans of different NSCLP populations (19,21,25,26,28). Analysis of STR D16S3037 in our dataset provided evidence for an association with NSCLP (P = 0.00063).…”

Section: Discussionsupporting

confidence: 60%

“…Linkage disequilibrium (LD) analysis identified STR marker D16S3037, in the 16q24.1 chromosomal region, that was significantly associated with NSCLP (P = 0.00063). Results from three other NSCLP genome scans and one targeted genome scan have also suggested that a NSCLP candidate gene lies on the long arm of chromosome 16, between 16q21-24, which includes D16S3037 (19,21,25,28).…”

Section: Introductionmentioning

confidence: 99%

“…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%

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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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Section: Discussionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CRISPLD2: a novel NSCLP candidate gene

Chiquet¹,

Lidral²,

Stal³

et al. 2007

Human Molecular Genetics

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“…The first CL/P scan was performed on 92 British sibpairs and identified a total of nine regions with suggestive results [49]. This has been followed by five additional scans of varying size (Table 2) [20,24,[49][50][51][52][53][54]. In general, the results have been modest with the exception of a log odds ratio (LOD) score of 3.0 at 17p13.1 in a scan of two large Syrian families [50].…”

Section: Genome Scans Identify Novel Locimentioning

confidence: 99%

“…This has been followed by five additional scans of varying size (Table 2) [20,24,[49][50][51][52][53][54]. In general, the results have been modest with the exception of a log odds ratio (LOD) score of 3.0 at 17p13.1 in a scan of two large Syrian families [50]. The most consistent loci are 2p13 (TGFA), 2q35-q37, 3p21-p24, 4q32-q33, 6p23-p25, 9q22-q33, 14q12-q31, and 18q11-q12, with the remaining 23 loci being unique to the population studied.…”

Section: Genome Scans Identify Novel Locimentioning

confidence: 99%

Progress toward discerning the genetics of cleft lip

Lidral

Moreno

2005

Current Opinion in Pediatrics

111

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Purpose of review-Orofacial clefts are common birth defects with a known genetic component to their etiology. Most orofacial clefts are nonsyndromic, isolated defects, which can be separated into two different phenotypes: (1) cleft lip with or without cleft palate and (2) cleft palate only. Both are genetically complex traits, which has limited the ability to identify disease loci or genes. The purpose of this review is to summarize recent progress of human genetic studies in identifying causal genes for isolated or nonsyndromic cleft lip with or without cleft palate.Recent findings-The results of multiple genome scans and a subsequent meta-analysis have significantly advanced our knowledge by revealing novel loci. Furthermore, candidate gene approaches have identified important roles for IRF6 and MSX1. To date, causal mutations with a known functional effect have not yet been described.Summary-With the implementation of genome-wide association studies and inexpensive sequencing, future studies will identify disease genes and characterize both gene-environment and gene-gene interactions to provide knowledge for risk counseling and the development of preventive therapies.

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Variation in IRF6 contributes to nonsyndromic cleft lip and palate

Blanton

Cortez

Stal

et al. 2005

American J of Med Genetics Pt A

128

106

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Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common craniofacial birth defect which results in lifelong medical and social consequences. While there have been a number of attempts to identify the genes responsible for this disorder, the results have not been consistent among populations and no single gene has been identified as playing a major susceptibility role. Van der Woude syndrome, a disorder characterized by lower‐lip pits with or without cleft lip/palate, results in many cases from mutations in the interferon regulatory factor 6 (IRF6) gene. Recently, Zucchero et al. [2004: N Engl J Med 351:769–780] detected an association between SNPs in IRF6 and NSCLP in a number of different populations. A subsequent study by Scapoli et al. [2005: Am J Hum Genet 76:180–183] confirmed this association in an Italian population. We examined the same SNPs as Scapoli et al. [2005] in our large, well‐characterized sample of NSCLP families and trios, and also detected an altered transmission of IRF6 alleles. This additional confirmation further strengthens the IRF6 association and suggests that IRF6 plays a role in NSCLP susceptibility. © 2005 Wiley‐Liss, Inc.

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A genome‐wide scan for loci predisposing to non‐syndromic cleft lip with or without cleft palate in two large Syrian families

Cited by 50 publications

References 78 publications

CRISPLD2: a novel NSCLP candidate gene

CRISPLD2: a novel NSCLP candidate gene

Progress toward discerning the genetics of cleft lip

Variation in IRF6 contributes to nonsyndromic cleft lip and palate

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