Whole‐genome sequencing in a pair of monozygotic twins with discordant cleft lip and palate subtypes

Takahashi, Masahiro; Hosomichi, Kazuyoshi; Yamaguchi, Tetsutaro; Nagahama, Ryo; Yoshida, Hiroshi; Maki, Koutaro; Marazita, Mary L.; Weinberg, Seth M.; Tajima, Atsushi

doi:10.1111/odi.12910

Cited by 6 publications

(5 citation statements)

References 34 publications

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“…Multiple large-scale genome-wide association studies (GWASs) have been performed in nonsyndromic OFC cohorts to identify $45 genetic loci that collectively account for $25% of the estimated liability to OFCs. [7][8][9][10][11] Rare coding variants have been examined by exome and limited genome sequencing studies, [12][13][14][15][16][17][18][19] but these approaches have not yet been widely applied, and sample sizes and populations have been limited to about 100 or fewer families with individuals affected by OFCs. In this manuscript, we focus on DNMs as one understudied class of rare variants influencing an individual's risk to OFCs.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios

Bishop

Perez

Sun

et al. 2020

The American Journal of Human Genetics

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Although de novo mutations (DNMs) are known to increase an individual's risk of congenital defects, DNMs have not been fully explored regarding orofacial clefts (OFCs), one of the most common human birth defects. Therefore, whole-genome sequencing of 756 childparent trios of European, Colombian, and Taiwanese ancestry was performed to determine the contributions of coding DNMs to an individual's OFC risk. Overall, we identified a significant excess of loss-of-function DNMs in genes highly expressed in craniofacial tissues, as well as genes associated with known autosomal dominant OFC syndromes. This analysis also revealed roles for zinc-finger homeobox domain and SOX2-interacting genes in OFC etiology.

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Section: Introductionmentioning

confidence: 99%

Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios

Bishop

Perez

Sun

et al. 2020

The American Journal of Human Genetics

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“…Standard cephalometry and whole-genome sequencing were used to examine craniofacial morphologic characteristics and potential genetic variations. The result of this study was that the lack of hereditary differences and the observed disparities in craniofacial morphology between the monozygotic twins may be directly attributed to the effects of the orofacial cleft on growth and/or differences in surgical history (32).…”

Section: Discussionmentioning

confidence: 85%

“…The concordance percentage of 40-60% in monozygotic twins is higher than the rate of 3-5% in dizygotic twins and also denotes a robust, consistent, and reliable inheritance pattern (30,31). Whole-genome sequencing in a pair of monozygotic twins with discordant cleft lip and palate subtypes showed that twin 1 had nonsyndromic bilateral cleft lip and palate, while twin 2 had nonsyndromic bilateral cleft lip and unilateral left-sided cleft alveolus (32). There was no oro-facial cleft in either of the parent.…”

Section: Discussionmentioning

confidence: 90%

Genetic Analysis of TPM1 Gene Polymorphism (rs11071720) in Patients with Non-Syndromic Cleft Lip/Palate in the South Indian Population. A Case Control Study

Murugesan,

Felicita,

Jayaseelan

2024

Odovtos - Int J Dent Sc

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The aim of this study was to find out if there was an association between TPM1 gene polymorphism (rs11071720) and non-syndromic cleft lip and palate in humans. Twenty five patients with non-syndromic cleft lip and palate (NSCL/P) and twenty five healthy patients as controls were enrolled in the study. Whole blood drawn from the participants was used to obtain genomic DNA. Sequence specific primers were used to amplify the region spanning the polymorphic site of the TPM1 gene using polymerase chain reaction (PCR). The genotype of the subjects was identified employing the RFLP technique. The genotype and allele frequency distributions in the non-syndromic cleft lip and cleft palate patients and control groups were compared using Chi-square test. In the NSCL/P, the genotype in the order from highest to lowest frequency was TC (48%), followed by CC (32%) and TT (20%). Although the genotype frequency of the case and the control groups were found to be in agreement with Hardy Weinberg Equilibrium, the genotype frequencies TC, CC and TT of the polymorphism (rs11071720) among the two groups were not statistically significant which was evident from the p-value 0.8472. No significant association was found between TPM1 gene (rs11071720) polymorphism and NSCL/P.

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“…8 However, other investigations, using different technical approaches, were unsuccessful to identify genetic differences in discordant nsCL/P twin pairs. 9–12…”

Section: Introductionmentioning

confidence: 99%

“…8 However, other investigations, using different technical approaches, were unsuccessful to identify genetic differences in discordant nsCL/P twin pairs. [9][10][11][12] Discordant MZ twin pairs, that are informative in respect to variability of phenotypic expression, epigenetics, and postzygotic mutagenesis, may represent an alternative approach to identify genes in inherited disorders. We hypothesized that postzygotic de novo mutations could cause discordant MZ twin pairs for nsCL/P, that are otherwise genetically identical.…”

Section: Introductionmentioning

confidence: 99%

Copy number variation analysis of twin pairs discordant for cleft lip with or without cleft palate

Scapoli

Palmieri

Curá

et al. 2019

Int J Immunopathol Pharmacol

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Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a frequent orofacial malformation. The comparison of concordance rate observed in monozygotic and dizygotic twins supports high level of heritability and a strong genetic component. However, phenotype concordance for orofacial cleft in monozygotic twins is about 50%. The aim of the present investigation was to detect postzygotic events that may account for discordance in monozygotic twins. High-density SNP microarrays hybridization was used to genotype two pairs of monozygotic twins discordant for nsCL/P. Discordant SNP genotypes and copy number variants were analyzed to identify genetic differences responsible of phenotype discrepancy. A number of differences were observed, none involving known nsCL/P candidate genes or genomic regions. Considering the limitation of the study, related to the small sample size and to the large-scale investigation method, the results suggest that the detection of discordant events in other monozygotic twin pairs would be remarkable and warrant further investigations.

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Whole‐genome sequencing in a pair of monozygotic twins with discordant cleft lip and palate subtypes

Cited by 6 publications

References 34 publications

Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios

Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios

Genetic Analysis of TPM1 Gene Polymorphism (rs11071720) in Patients with Non-Syndromic Cleft Lip/Palate in the South Indian Population. A Case Control Study

Copy number variation analysis of twin pairs discordant for cleft lip with or without cleft palate

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