Biomaterial Database

The novel bilirubin/phenol UDP-glucuronosyltransferase UGT1 gene locus: implications for multiple nonhemolytic familial hyperbilirubinemia phenotypes. 1992

I S Owens, and J K Ritter

Section of Genetic Disorders of Drug Metabolism, National Institute of Child Health and Human Development, Bethesda, MD 20892.

At least three types of congenital nonhemolytic unconjugated hyperbilirubinemias, including the rare Crigler-Najjar (CN) diseases (Types I or II) and Gilbert's syndrome (affecting 6% of the population) are associated with either absent or reduced hepatic UDP-glucuronosyltransferase (transferase) activity towards the potentially toxic endogenous acceptor, bilirubin. Here, we review the biochemical studies associated with these deficiencies. Accumulated evidence from studies with an animal model of CN Type I syndrome, the Gunn strain of hyperbilirubinemic rats, suggested that multiple isozymes are absent. These confounding observations have been clarified by a flurry of reports which have revealed the molecular basis for the complex disease phenotype in the Gunn rat and by the isolation and description of a novel human gene complex, UGT1, which encodes multiple and independently-regulated transferase isozymes that contain identical carboxyl terminal regions (246 amino acids). Finally, we discuss the implications of the gene organization and genetic defects determined for four different CN Type I individuals as a basis for a model which explains the inheritance pattern and genotypes of other familial unconjugated hyperbilirubinemias.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010375	Pedigree	The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.	Family Tree,Genealogical Tree,Genealogic Tree,Genetic Identity,Identity, Genetic,Family Trees,Genealogic Trees,Genealogical Trees,Genetic Identities,Identities, Genetic,Tree, Family,Tree, Genealogic,Tree, Genealogical,Trees, Family,Trees, Genealogic,Trees, Genealogical
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D011911	Rats, Gunn	Mutant strain of Rattus norvegicus which is used as a disease model of kernicterus.	Gunn Rat,Gunn Rats,Rat, Gunn
D003001	Cloning, Molecular	The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.	Molecular Cloning
D003414	Crigler-Najjar Syndrome	A familial form of congenital hyperbilirubinemia transmitted as an autosomal recessive trait. It is characterized by icterus and brain damage caused by a glucuronyl transferase deficiency in the liver and faulty bilirubin conjugation.	Crigler Najjar Syndrome,Crigler Najjar Syndrome, Type 1,Crigler-Najar Syndrome,Crigler-Najjar Syndrome, Type I,Familial Nonhemolytic Unconjugated Hyperbilirubinemia,Hereditary Unconjugated Hyperbilirubinemia,Crigler Najar Syndrome,Crigler Najjar Syndrome, Type I,Crigler Najjar Syndromes,Hereditary Unconjugated Hyperbilirubinemias,Hyperbilirubinemia, Hereditary Unconjugated,Najjar Syndrome, Crigler,Syndrome, Crigler Najjar,Unconjugated Hyperbilirubinemia, Hereditary
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005260	Female		Females
D005810	Multigene Family	A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)	Gene Clusters,Genes, Reiterated,Cluster, Gene,Clusters, Gene,Families, Multigene,Family, Multigene,Gene Cluster,Gene, Reiterated,Multigene Families,Reiterated Gene,Reiterated Genes
D005878	Gilbert Disease	A benign familial disorder, transmitted as an autosomal dominant trait. It is characterized by low-grade chronic hyperbilirubinemia with considerable daily fluctuations of the bilirubin level.	Constitutional Liver Dysfunction,Familial Nonhemolytic Jaundice,Gilbert Syndrome,Gilbert's Disease,Gilbert's Syndrome,Gilbert-Lereboullet Syndrome,Hyperbilirubinemia 1,Hyperbilirubinemia I,Hyperbilirubinemia, Arias Type,Meulengracht Syndrome,Unconjugated Benign Bilirubinemia,Arias Type Hyperbilirubinemia,Arias Type Hyperbilirubinemias,Disease, Gilbert,Disease, Gilbert's,Gilberts Disease,Gilberts Syndrome,Hyperbilirubinemia 1s,Hyperbilirubinemias, Arias Type,Syndrome, Gilbert,Syndrome, Gilbert's