title: A novel gene encoding a TIG multiple domain protein is a positional candidate for autosomal recessive polycystic kidney disease.
abstract: Autosomal recessive polycystic kidney disease (ARPKD) is a common hereditary renal cystic disease in infants and children. By genetic linkage analyses, the gene responsible for this disease, termed polycystic kidney and hepatic disease 1 (PKHD1), was mapped on human chromosome 6p21.1-p12, and has been further localized to a 1-cM genetic interval flanked by the D6S1714/D6S243 (telomeric) and D6S1024 (centromeric) markers. We recently identified a novel gene in this genetic interval from kidney cDNA, using cloning strategies. The gene PKHD1 (PKHD1-tentative) encodes a novel 3396-amino-acid protein with no apparent homology with any known proteins. We named its gene product "tigmin" because it contains multiple TIG domains, which usually are seen in proteins containing immunoglobulin-like folds. PKHD1 encodes an 11.6-kb transcript and is composed of 61 exons spanning an approximately 365-kb genomic region on chromosome 6p12-p11.2 adjacent to the marker D6S1714. Northern blot analyses demonstrated that the gene has discrete bands with one peak signal at approximately 11 kb, indicating that PKHD1 is likely to have multiple alternative transcripts. PKHD1 is highly expressed in adult and infant kidneys and weakly expressed in liver in northern blot analysis. This expression pattern parallels the tissue involvement observed in ARPKD. In situ hybridization analysis further revealed that the expression of PKHD1 in the kidney is mainly localized to the epithelial cells of the collecting duct, the specific tubular segment involved in cyst formation in ARPKD. These features of PKHD1 make it a strong positional candidate gene for ARPKD.
authors.affiliation: Departments of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Huaqi
authors.initials: H
authors.lastname: Xiong
authors.forename: Yongxiong
authors.initials: Y
authors.lastname: Chen
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yi
authors.forename: Karen
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Gilbert
authors.initials: G
authors.lastname: Moeckel
authors.forename: Joseph
authors.initials: J
authors.lastname: Cheung
authors.forename: Dan
authors.initials: D
authors.lastname: Liang
authors.forename: Kyi
authors.initials: K
authors.lastname: Tham
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Xu
authors.forename: Xing-Zhen
authors.initials: XZ
authors.lastname: Chen
authors.forename: York
authors.initials: Y
authors.lastname: Pei
authors.forename: Zhizhuang Jeo
authors.initials: ZJ
authors.lastname: Zhao
authors.forename: Guanqing
authors.initials: G
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics*; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
chemical_list: C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface