title: Cloning and characterization of FAM13A1--a gene near a milk protein QTL on BTA6: evidence for population-wide linkage disequilibrium in Israeli Holsteins.
abstract: A cluster of genes coding for proteins of the extracellular matrix (ECM) containing sequence motifs essential for integrin-receptor interactions is located on HSA4q21 and on BTA6, within the critical region of a quantitative trait locus (QTL) affecting milk protein production. Genes within this cluster are involved in the formation of bone and lobuloalveolar structures in mammary gland and in kidney function. We cloned a bovine gene neighboring this ECM cluster, termed FAM13A1, the first member of a novel gene family (FAM13). A short predominant 5.1-kb mRNA variant capable of encoding 697 amino acids is transcribed from 18-exon orthologous genes in human and mouse. All putative protein orthologs contained a bipartite nuclear-localization signal and two coil-coiled domains. We detected two other FAM13 paralogs, C5ORF5 and FAM13C1, on HSA5q31 and HSA10q21, respectively. All FAM13 paralogs produce transcripts that are complementary to adjacent genes, suggesting that antisense transcription may regulate their functions. The structure of a longer 5.9-kb variant, FAM13A1_v2, that has an extra 7-exon putative RhoGAP domain at the N-terminus provides further clues to FAM13 function. Analysis of 400 bulls revealed a population-wide linkage disequilibrium between FAM13A1 polymorphisms and the QTL.
authors.affiliation: Institute of Animal Sciences, Agricultural Research Organization, The Volcani Center, Bet Dagan 50250, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Cohen
authors.forename: Moshe
authors.initials: M
authors.lastname: Reichenstein
authors.forename: Annelie
authors.initials: A
authors.lastname: Everts-van der Wind
authors.forename: Jun
authors.initials: J
authors.lastname: Heon-Lee
authors.forename: Moshe
authors.initials: M
authors.lastname: Shani
authors.forename: Harris A
authors.initials: HA
authors.lastname: Lewin
authors.forename: Joel I
authors.initials: JI
authors.lastname: Weller
authors.forename: Micha
authors.initials: M
authors.lastname: Ron
authors.forename: Eyal
authors.initials: E
authors.lastname: Seroussi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle / Q000235:genetics*; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000737:chemistry; D005787:Gene Frequency; D023281:Genomics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007557:Israel; D015810:Linkage Disequilibrium / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D008894:Milk Proteins / Q000737:chemistry* / Q000235:genetics*; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017434:Protein Structure, Tertiary; D040641:Quantitative Trait Loci / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D008894:Milk Proteins; D012333:RNA, Messenger; C085379:rho GTPase-activating protein