Targeted scan of fifteen regions for nonsyndromic cleft lip and palate in Filipino families

Schultz, R. E.; Cooper, Margaret E.; Daack‐Hirsch, Sandra; Shi, Min; Nepomucena, B.; Graf, K. A.; O’Brien, Erin; O'Brien, Sarah; Marazita, Mary L.; Murray, Jeffrey C.

doi:10.1002/ajmg.a.20424

Cited by 68 publications

(52 citation statements)

References 32 publications

(49 reference statements)

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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%

“…An additional study population consisted of 64 multiplex NSCLP families and 155 simplex parent-child NSCLP trios who were recruited from the Clinica Noel in Medellín, Colombia as previously described (28). All cases had isolated clefting and no syndromic cases of CL/P were included.…”

Section: Study Population and Sample Preparationmentioning

confidence: 99%

“…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%

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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: Study Population and Sample Preparationmentioning

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 human gene encoding AP-2␣, TFAP2A, maps in close proximity to a region of chromosome 6p24 that is frequently involved in translocations and deletions associated with orofacial clefting (Davies et al, 1999a(Davies et al, ,b, 2004Topping et al, 2002;Schultz et al, 2004), raising the possibility that alterations in the long-range cis-regulatory sequences controlling TFAP2A expression might be responsible for congenital defects affecting human facial development. In the context of evolution, evidence from multiple species indicates that changes in the spatial and temporal regulation of the AP-2 family of genes, among others, might underlie the evolution of the vertebrate neural crest and, ultimately, the diversity of craniofacial skeleton (Meulemans and BronnerFraser, 2002;Holzschuh et al, 2003;Knight et al, 2003Knight et al, , 2005Luo et al, 2003;O'Brien et al, 2004).…”

Section: Regulation Of Tcfap2a In the Fnp And Lbm Are Controlled By Dmentioning

confidence: 99%

Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins

Donner

Williams

2006

Developmental Dynamics

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The AP-2 transcription factor family is linked with development of the head and limbs in both vertebrate and invertebrate species. Recent evidence has also implicated this gene family in the evolution of the neural crest in chordates, a critical step that allowed the development and elaboration of the vertebrate craniofacial skeleton. In mice, the inappropriate embryonic expression of one particular AP-2 gene, Tcfap2a, encoding AP-2␣, results in multiple developmental abnormalities, including craniofacial and limb defects. Thus, Tcfap2a provides a valuable genetic resource to analyze the regulatory hierarchy responsible for the evolution and development of the face and limbs. Previous studies have identified a 2-kilobase intronic region of both the mouse and human AP-2␣ locus that directs expression of a linked LacZ transgene to the facial processes and the distal mesenchyme of the limb bud in transgenic mice. Further analysis identified two highly conserved regions of ϳ200 -400 bp within this tissue-specific enhancer. We have now initiated a transgenic and biochemical analysis of the most important of these highly conserved regions. Our analysis indicates that although the sequences regulating face and limb expression have been integrated into a single enhancer, different cis-acting sequences ultimately control these two expression domains. Moreover, these studies demonstrate that a conserved STAT binding site provides a major contribution to the expression of Tcfap2a in the facial prominences. Developmental Dynamics 235: 1358 -1370, 2006.

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“…3,4 Their involvement is further supported by linkage and association studies in populations of different ethnic origin. [5][6][7][8] Although no deleterious mutation has been reported in TGFB3. 7,9 MSX1 has been suggested to function upstream of TGFB3 in the development of oral cleft.…”

Section: Introductionmentioning

confidence: 99%

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

et al. 2011

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Oral clefts are clinically and genetically heterogeneous disorders that are influenced by both genetic and environmental factors. The present family-based association study investigated the role of the MSX1 and TGFB3 genes in the etiology of non-syndromic oral cleft in a Malay population. No transmission distortion was found in the transmission disequilibrium analysis for either MSX1-CA or TGFB3-CA intragenic markers, whereas TGFB3-CA exhibited a trend to excess maternal transmission. In sequencing the MSX1 coding regions in 124 patients with oral cleft, five variants were found, including three known variants (A34G, G110G and P147Q) and two novel variants (M37L and G267A). The P147Q and M37L variants were not observed in 200 control chromosomes, whereas G267A was found in one control sample, indicating a very rare polymorphic variant. Furthermore, the G110G variant displayed a significant association between patients with non-syndromic cleft lip, with or without cleft palate, and normal controls (P¼0.001, odds ratio¼2.241, 95% confidence interval, 1.357-3.700). Therefore, these genetic variants may contribute, along with other genetic and environmental factors, to this condition. INTRODUCTIONOral clefts are clinically and genetically heterogeneous disorders, involving both genetic and environmental factors. MSX1 and TGFB3 have emerged as candidate genes for oral cleft, based on expression studies 1,2 and animal models. 3,4 Their involvement is further supported by linkage and association studies in populations of different ethnic origin. [5][6][7][8] Although no deleterious mutation has been reported in TGFB3. 7,9 MSX1 has been suggested to function upstream of TGFB3 in the development of oral cleft. 10 The aim of the current research was to investigate the genetic association of MSX1 and TGFB3 in a Malay population with non-syndromic orofacial cleft. The association study was performed using intragenic CA markers for MSX1 and TGFB3. The coding regions of MSX1 were also directly sequenced.

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Targeted scan of fifteen regions for nonsyndromic cleft lip and palate in Filipino families

Cited by 68 publications

References 32 publications

CRISPLD2: a novel NSCLP candidate gene

CRISPLD2: a novel NSCLP candidate gene

Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

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