Cloning of a novel human putative type Ia integral membrane protein mapping to 21q22.3.

The distal part of human chromosome 21q22.3 is exceptionally gene rich and contains several loci that have been linked to hereditary disorders. In the course of constructing an extensive transcript map for chromosome 21, we have isolated numerous coding segments in 21q22.3 that represent potential candidate genes in this region. Following this approach, we have cloned a novel single-copy gene (C21orf3) (HGMW-approved symbol C21orf1) expressed as a unique 2.69-kb mRNA in a wide range of tissues. We have precisely mapped C21orf3 by fiber FISH distal to marker D21S171. The C21orf3 gene encodes a predicted protein of 180 residues that does not share any sequence homology with other known proteins. C21orf3 harbors predicted structural features of a type Ia integral membrane protein and contains a tetrapeptide motif (YXRF) observed in several cell surface proteins involved in signal transduction. Although the function of C21orf3 is still unknown, this novel gene may play an important role in a cell trafficking mechanism.

[1]  L. Peltonen,et al.  An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains , 1997, Nature Genetics.

[2]  L. Peltonen,et al.  High-resolution physical and transcriptional mapping of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy locus on chromosome 21q22.3 by FISH. , 1997, Genome research.

[3]  R. Murray,et al.  Linkage studies in bipolar affective disorder with markers on chromosome 21. , 1996, Journal of affective disorders.

[4]  K. Gardiner,et al.  Base composition and gene distribution: critical patterns in mammalian genome organization. , 1996, Trends in genetics : TIG.

[5]  E. Lander,et al.  Genome maps 7. The human transcript map. Wall chart. , 1996, Science.

[6]  P. Deloukas,et al.  A Gene Map of the Human Genome , 1996, Science.

[7]  H. Friess,et al.  A pancreatic cancer-specific expression profile. , 1996, Oncogene.

[8]  B. Jasny.  Genome Maps 7: The Human Transcript Map , 1996 .

[9]  S. Antonarakis,et al.  Cloning of 559 potential exons of genes of human chromosome 21 by exon trapping. , 1996, Genome research.

[10]  M. Passos-Bueno,et al.  A gene which causes severe ocular alterations and occipital encephalocele (Knobloch syndrome) is mapped to 21q22.3. , 1996, Human molecular genetics.

[11]  R Staden,et al.  The staden sequence analysis package , 1996, Molecular biotechnology.

[12]  L. Farrer,et al.  Linkage of congenital recessive deafness (gene DFNB10) to chromosome 21q22.3. , 1996, American journal of human genetics.

[13]  M. Tessier-Lavigne,et al.  Physical mapping of the holoprosencephaly critical region in 21q22.3, exclusion of SIM2 as a candidate gene for holoprosencephaly, and mapping of SIM2 to a region of chromosome 21 important for Down syndrome. , 1995, American journal of human genetics.

[14]  D. Patterson,et al.  Molecular analysis and breakpoint definition of a set of human chromosome 21 somatic cell hybrids , 1995, Somatic cell and molecular genetics.

[15]  K. Gardiner,et al.  cDNA selection from 10 Mb of chromosome 21 DNA: efficiency in transcriptional mapping and reflections of genome organization. , 1995, Human molecular genetics.

[16]  A. Poustka,et al.  Model for a transcript map of human chromosome 21: isolation of new coding sequences from exon and enriched cDNA libraries. , 1995, Human molecular genetics.

[17]  K. Gardiner,et al.  Report of the seventh international workshop on human chromosome 21 mapping 1997 , 1995, Cytogenetic and Genome Research.

[18]  L. Peltonen,et al.  High resolution mapping using fluorescence in situ hybridization to extended DNA fibers prepared from agarose-embedded cells. , 1994, BioTechniques.

[19]  J. Cheng,et al.  Isolation and mapping of human chromosome 21 cDNA: progress in constructing a chromosome 21 expression map. , 1994, Genomics.

[20]  M. Kanehisa,et al.  A knowledge base for predicting protein localization sites in eukaryotic cells , 1992, Genomics.

[21]  R. Davis,et al.  Mutational analysis of the cytoplasmic tail of the human transferrin receptor. Identification of a sub-domain that is required for rapid endocytosis. , 1991, The Journal of biological chemistry.

[22]  R. Staden,et al.  A sequence assembly and editing program for efficient management of large projects. , 1991, Nucleic acids research.

[23]  J. Tainer,et al.  Transferrin receptor internalization sequence YXRF implicates a tight turn as the structural recognition motif for endocytosis , 1990, Cell.

[24]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[25]  Shinsei Minoshima,et al.  Positional cloning of the APECED gene , 1997, Nature Genetics.

[26]  L. Peltonen,et al.  An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21 , 1994, Nature Genetics.