Comparative studies of vertebrate iduronate 2-sulfatase (IDS) genes and proteins: evolution of A mammalian X-linked gene

نویسنده

  • Roger S. Holmes
چکیده

IDS is responsible for the lysosomal degradation of heparan sulfate and dermatan sulfate and linked to an X-linked lysosomal storage disease, mucopolysaccharidosis 2 (MPS2), resulting in neurological damage and early death. Comparative IDS amino acid sequences and structures and IDS gene locations were examined using data from several vertebrate genome projects. Vertebrate IDS sequences shared 60-99% identities with each other. Human IDS showed 47% sequence identity with fruit fly (Drosophila melanogaster) IDS. Sequence alignments, key amino acid residues, N-glycosylation sites and conserved predicted secondary and tertiary structures were also studied, including signal peptide, propeptide and active site residues. Mammalian IDS genes usually contained 9 coding exons. The human IDS gene promoter contained a large CpG island (CpG46) and 5 transcription factor binding sites, whereas the 3'-UTR region contained 5 miRNA target sites. These may contribute to IDS gene regulation of expression in the brain and other neural tissues of the body. An IDS pseudogene (IDSP1) was located proximally to the IDS gene on the X-chromosome in primate genomes. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate IDS gene. These suggested that IDS has originated in an invertebrate ancestral genome and retained throughout vertebrate evolution and conserved on marsupial and eutherian X-chromosomes, with the exception of rat Ids on chromosome 8.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Hunter syndrome: isolation of an iduronate-2-sulfatase cDNA clone and analysis of patient DNA.

Iduronate 2-sulfatase (IDS, EC 3.1.6.13) is required for the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations causing IDS deficiency in humans result in the lysosomal storage of these glycosaminoglycans and Hunter syndrome, an X chromosome-linked disease. We have isolated and sequenced a 2.3-kilobase cDNA clone coding for the entire sequence of human IDS. Analysis of the...

متن کامل

Molecular Analyses in Families with Hunter Syndrome Indicate Unequal Male and Female Mutation Rates in the Iduronate-2-Sulfatase Gene

Molecular diagnosis for patients with mucopolysaccharidosis type II (MPS II, Hunter syndrome) has detected a spectrum of mutations including large deletions, intragenic rearrangements, recurrent nucleotide substitutions at CpG sites, and high proportion of novel point mutations in the X-linked iduronate-2-sulfatase (IDS) gene. The mutational heterogeneity and the X-linked inheritance make the I...

متن کامل

Severe phenotype in MPS II patients associated with a large deletion including contiguous genes.

Hunter disease or mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal disorder caused by the deficiency of iduronate-2-sulfatase, which is involved in the catabolism of the glycosaminoglycans (GAGs) heparan and dermatan sulphate. Our aim was to analyze three patients with severe Hunter syndrome that showed a total deletion of the iduronate-2-sulphatase (IDS) gene, after ex...

متن کامل

A novel iduronate 2-sulfatase mutation in a Chinese family with mucopolysaccharidosis type II.

BACKGROUND Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome) is an X-linked multisystem disorder resulting from the defective activity of the enzyme iduronate-2-sulfatase (IDS). Genetic testing is crucial in clarifying and diagnosing different types of MPS diseases. In this paper we report a novel IDS nonsense mutation resulting in MPS II in several patients from a Chinese f...

متن کامل

Identification of 17 novel mutations in 40 Argentinean unrelated families with mucopolysaccharidosis type II (Hunter syndrome)

Mucopolysaccharidosis type II (MPSII) is an X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulfatase (IDS). The human IDS gene is located in chromosome Xq28. This is the first report of genotype and phenotype characterization of 49 Hunter patients from 40 families of Argentina. Thirty different alleles have been identified, and 57% were novel. The frequency o...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2017