Elsevier

Genomics

Volume 84, Issue 3, September 2004, Pages 536-549
Genomics

Analysis of the human VPS13 gene family

https://doi.org/10.1016/j.ygeno.2004.04.012Get rights and content

Abstract

The gene mutated in chorea-acanthocytosis (CHAC; approved gene symbol VPS13A) encodes chorein, a protein similar to yeast Vps13p. We detected several similar putative human proteins by BLAST analysis of chorein. We characterized the structure of three new genes encoding these CHAC-similar proteins, located on chromosomes 1p36, 8q22, and 15q21. The most similar gene in yeast to all four human genes is Vps13, and therefore the human genes were named VPS13A (CHAC, 9q21), VPS13B (8q22), VPS13C (15q21), and VPS13D (1p36). VPS13B has recently been reported as COH1, altered in Cohen syndrome. For each gene, we describe several alternative splicing variants; at least two transcripts per gene are major forms. The expression pattern of these genes is ubiquitous, with some tissue-specific differences between several transcript variants. Protein sequence comparisons suggest that intramolecular duplications have played an important role in the evolution of this gene family.

Section snippets

Identification and structure of human genes similar to CHAC

We performed a BLAST analysis of chorein variant A against DNA and protein databases, and a number of hypothetical proteins showed high similarity: KIAA1421, FLJ20136, and FLJ10381 on chromosome 15q21.3; FLJ20583 and KIAA0532 on 8q22; and FLJ10619 and KIAA0453 on 1p36. The different proteins encoded by potential genes in each chromosome region showed similarity with a different region of chorein. These results suggested that there were three genes similar to CHAC, one on each of the

Discussion

We report here the characterization of a human gene family homologous to yeast Vps13. Rampoldi et al. [1] and Ueno et al. [2] reported VPS13A (formerly CHAC) as the gene that is mutated in the neurodegenerative disorder ChAc. We have identified three new genes, VPS13B, VPS13C, and VPS13D, encoding proteins similar to chorein. VPS13B has recently been reported as COH1 [7], altered in the recessive disorder Cohen syndrome.

Identification and structure determination of VPS13 genes

Chorein was compared against the databases using BLAST facilities at EMBL-EBI http://www.ebi.ac.uk/blast2/) and NCBI http://www.ncbi.nlm.nih.gov/BLAST/). The detected human proteins were located on the genome using the MapViewer facility http://www.ncbi.nlm.nih.gov/mapview/) for Homo sapiens, build 31, and the mRNA sequences available aligning in the respective region were obtained following the Evidence Viewer link. Gaps in the cDNA sequence were transiently filled according to GenomeScan

Acknowledgements

This work was supported by the Wellcome Trust. A.V.-B. is supported by a Marie Curie postdoctoral fellowship. A.V. was supported by a predoctoral fellowship from the Italian Ministero dell'Universita' e della Ricerca Scientifica e Tecnologica. C.D.-S. was supported by a Wellcome Trust Prize Studentship. A.P.M. is a Wellcome Trust Principal Research Fellow.

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  • Cited by (0)

    Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession Nos. AJ608769, AJ626859, AJ608772, AJ608773, AJ608770, AJ608771, AJ626860, AJ626861, AJ608774, and AJ608775.

    1

    These two authors contributed equally to this article.

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