Dataset Information

Genome-wide linkage analysis and whole-genome sequencing identify a recurrent SMARCAD1 variant in a unique Chinese family with Basan syndrome.

ABSTRACT: Basan syndrome is a rare autosomal dominant genodermatosis, characterized by rapidly healing congenital acral bullae, congenital milia and lack of fingerprints. A mutation in the SMARCAD1 gene was recently reported to cause Basan syndrome in one family. Here, we present a large Chinese family with Basan syndrome; some patients presented with hyperpigmentation and knuckle pads in addition to previously reported clinical manifestations. We used genome-wide linkage analysis and whole-genome sequencing (WGS) to identify the pathogenic gene in this unique pedigree. Genome-wide linkage analysis successfully mapped the candidate gene to 4p15.31-4p14 and 4q13.2-4q23. The maximal LOD score was 3.01. WGS in one patient identified a splice variant (c.378+1G>T) in the SMARCAD1 gene (NG_031945.1) that was confirmed by Sanger sequencing. Co-segregation of the variant was confirmed in this pedigree. The same variant was recently found to be associated with isolated adermatoglyphia (ADG) in another family, suggesting that this variant is causative for both Basan syndrome and autosomal dominant ADG (OMIM 136?000). This indicates that ADG and Basan syndrome may be the phenotypic variants of the same disease. Further studies should be performed to elucidate the pathogenic mechanisms induced by this variant. This report increases the phenotypic spectrum of Basan syndrome and furthers our understanding of the genetic basis of this disease. Our results also highlight the power of combining WGS and genome-wide linkage analysis in identifying causative genes in pedigrees with a genetic disorder.

SUBMITTER: Li M

PROVIDER: S-EPMC4989204 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Genome-wide linkage analysis and whole-genome sequencing identify a recurrent SMARCAD1 variant in a unique Chinese family with Basan syndrome.

Li Ming M Wang Jianbo J Li Zhenlu Z Zhang Jia J Ni Cheng C Cheng Ruhong R Yao Zhirong Z

European journal of human genetics : EJHG 20160302 9

Basan syndrome is a rare autosomal dominant genodermatosis, characterized by rapidly healing congenital acral bullae, congenital milia and lack of fingerprints. A mutation in the SMARCAD1 gene was recently reported to cause Basan syndrome in one family. Here, we present a large Chinese family with Basan syndrome; some patients presented with hyperpigmentation and knuckle pads in addition to previously reported clinical manifestations. We used genome-wide linkage analysis and whole-genome sequenc ...[more]

PMID: 26932190

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Project description:BackgroundNext generation sequencing (NGS) has traditionally been performed by large genome centers, but in recent years, the costs for whole-genome sequencing (WGS) have decreased substantially. With the introduction of smaller and less expensive "desktop" systems, NGS is now moving into the general laboratory. To evaluate the Ion Proton system for WGS we sequenced four Chinese Crested dogs and analyzed the data quality in terms of genome and exome coverage, the number of detected single nucleotide variants (SNVs) and insertions and deletions (INDELs) and the genotype concordance with the Illumina HD canine SNP array. For each of the four dogs, a 200 bp fragment library was constructed from genomic DNA and sequenced on two Ion PI chips per dog to reach mean coverage of 6-8x of the canine genome (genome size ≈ 2.4 Gb).ResultsOn average, each Ion PI chip yielded approximately 73.3 million reads with a mean read length of 130 bp (~9.5 Gb sequence data) of which 98.5 % could be aligned to the canine reference genome (CanFam3.1). By sequencing a single dog using one fragment library and two Ion PI chips, on average 80 % of the genome and 77 % exome was covered by at least four reads. After removing duplicate reads (20.7 %) the mean coverage across the whole genome was 6x. Using sequence data from all four individuals (four fragment libraries and eight Ion PI chips) the genome and exome coverage could be further increased to 97.2 and 94.3 %, respectively. We detected 4.83 million unique SNPs and 6.10 million unique INDEL positions across all individuals. A comparison between SNP genotypes detected with the WGS and the 170 K Illumina HD canine SNP array showed 90 % concordance.ConclusionsWe have evaluated whole-genome sequencing on the Ion Proton system for genetic variant detection in four Chinese crested dogs. Even though INDEL calling with Ion Proton data is challenging due to specific platform errors, in case of SNP calling it can serve as an alternative to other next-generation sequencing platforms and SNP genotyping arrays, in studies aiming to identify causative mutations for rare monogenic diseases. In addition, we have identified new genetic variants of the Chinese Crested dog that will contribute to further whole-genome sequencing studies aimed to identify mutations associated with monogenic diseases with autosomal recessive inheritance.

Dataset Information

Genome-wide linkage analysis and whole-genome sequencing identify a recurrent SMARCAD1 variant in a unique Chinese family with Basan syndrome.

Publications

Genome-wide linkage analysis and whole-genome sequencing identify a recurrent SMARCAD1 variant in a unique Chinese family with Basan syndrome.

Similar Datasets

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