Genomic organization of the siglec gene locus on chromosome 19q13.4 and cloning of two new siglec pseudogenes.
The sialic acid binding immunoglobulin-like lectin (Siglec) family of genes is a recently described member of the immunoglobulin superfamily. Within this Siglec family there is a subgroup of genes which bear a high degree of homology with Siglec-3 (CD33), thus designated the Siglec-3-like subgroup of Siglecs. While their mRNA structure has been reported, the full genomic organization of these genes, is not known. Genes of this subgroup have been mapped to chromosome 19q13.4, primarily through in situ hybridization. Through analysis of several bacterial artificial chromosome (BAC) clones, we studied an approximate 700 kb region that encompasses the putative Siglec gene locus on chromosome 19q13.4. We established the first detailed map of the locus, which contains 8 Siglec and Siglec-like genes. Our map shows the relative position of all genes and the precise distances between them, along with the direction of transcription of each gene. To our knowledge, this is the first report that describes the full genomic organization of all members of the CD33-like subgroup of Siglecs, including the promoter sequences of all genes. Members of this subfamily exhibit two patterns of organization of the signal peptide, which is followed by one V-set domain (except for the long form of the siglecL1 gene). Exons containing the C2-set domains are all comparable in size and are separated by linker exons. The transmembrane domain is encoded for by a separate exon of almost the same size in all genes. The total number of exons differs according to the number of C2-set Ig domains, but intron phases are identical. The cytoplasmic domain is always encoded by two exons. We further identified two new Siglec pseudogenes in this locus, and analyzed their tissue expression pattern and their structural features.
Yousef
George M
GM
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5.
Ordon
Michael H
MH
Foussias
George
G
Diamandis
Eleftherios P
EP
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D015815:Cell Adhesion Molecules; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D037102:Lectins; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D011544:Pseudogenes / Q000235:genetics*; D015183:Restriction Mapping; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D051918:Sialic Acid Binding Ig-like Lectin 2; D063268:Sialic Acid Binding Ig-like Lectin 3
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D015214:Antigens, Differentiation, Myelomonocytic; C497867:CD22 protein, human; C571163:CD33 protein, human; D015815:Cell Adhesion Molecules; D037102:Lectins; C120775:SIGLEC6 protein, human; C402206:SIGLEC7 protein, human; D051918:Sialic Acid Binding Ig-like Lectin 2; D063268:Sialic Acid Binding Ig-like Lectin 3; D004247:DNA