Abstract:
:Protoporphyria is an autosomal dominant disease in man in which protoporphyrin accumulated because of a defect in heme synthase (ferrochelatase) activity. A disease has been described in cattle that has the same manifestations as does the human disease. We measured heme synthase activity in sonicates of cultured skin fibroblasts and whole liver homogenates from animals with protoporphyria, their unaffected parents, and normal cattle in order to examine the mode of inheritance and compare it with human protoporphyria. The mean activity (+/- SEM) in fibroblasts from the three groups was 2.0 +/- 0.4, 47 +/- 12, and 149 +/- 10 pmol heme formed/mg protein per hr, respectively, consistent with autosomal recessive inheritance. Similarly, the levels of heme synthase activity in livers of the parents were intermediate to those of normal animals and of animals with protoporphyria. When compared with normal human fibroblasts and liver, the specific activity of heme synthase in normal bovine tissue was significantly higher. These studies indicate that manifestations of protoporphyria do not occur in cattle unless the animal is homozygous for the gene defect, whereas in humans, the heterozygous condition is sufficient. This is probably because the specific activity of heme synthase in cells of heterozygous animals is not reduced to a level that significantly alters heme metabolism.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Bloomer JR,Morton KO,Reuter RJ,Ruth GRsubject
Has Abstractpub_date
1982-03-01 00:00:00pages
322-30issue
2eissn
0002-9297issn
1537-6605journal_volume
34pub_type
杂志文章abstract::The genetic map in the region of human chromosome 7 that harbors the gene for cystic fibrosis (CF) has been refined by multilocus linkage studies in an expanded database including a large set of normal families. Six loci known to be linked to CF were examined: MET, an oncogene; COL1A2, collagen, TCRB, T-cell-receptor ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::Revertant mosaicism is an infrequently observed phenomenon caused by spontaneous correction of a pathogenic allele. We have observed such reversions caused by mitotic recombination of mutant TERC (telomerase RNA component) alleles in six patients from four families affected by dyskeratosis congenita (DC). DC is a mult...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.01.004
更新日期:2012-03-09 00:00:00
abstract::Human neuroblastoma cells often are monosomic for the distal portion of 1p (1p36). We report that the deleted 1p material in cells of neuroblastoma lines is preferentially replaced by material from chromosome 17, resulting from an unbalanced 1;17 translocation. Chromosome 17 often acquires instability, followed by the...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The common 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism causes decreased activity of this enzyme and can be associated with mild-to-moderate hyperhomocysteinemia in homozygotes, particularly when there is folic acid deficiency, as well as with vascular dementia, arterial thrombosis, venous throm...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/338932
更新日期:2002-03-01 00:00:00
abstract::The autosomal dominant cerebellar ataxias (ADCA) type I are a group of neurological disorders that are clinically and genetically heterogeneous. Two genes implicated in the disease, SCA1 (spinal cerebellar ataxia 1) and SCA2, are already localized. We have mapped a third locus to chromosome 14q24.3-qter, by linkage an...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::The linkage of polymorphic DNA markers on chromosome 7 to cystic fibrosis (CF) was examined in two pedigrees and a number of smaller nuclear families. The pedigrees are multigenerational and together consist of more than 300 members including 30 affected individuals, while the nuclear families each have two generation...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract::One widely used measure of genetic similarity for pairs of relatives is gene identity-by-descent (IBD) sharing. Genes that are copies of a single gene in a common ancestor of the individuals who now carry them are said to be IBD. One obvious extension of the IBD concept is IBD gene(s) shared by more than two individua...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::It has been proposed that gluten sensitive enteropathy (GSE) results from the interaction of two loci: one locus linked to HLA and associated with dominant inheritance, and the other, a non-HLA-linked GSE-associated B-cell alloantigen, exhibiting recessive inheritance. We have shown in previous analyses that a two-loc...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::Loss-of-heterozygosity (LOH) studies have implicated one or more chromosome 11 tumor-suppressor gene(s) in the development of cutaneous melanoma as well as a variety of other forms of human cancer. In the present study, we have identified multiple independent critical regions on this chromosome by use of homozygosity ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302999
更新日期:2000-08-01 00:00:00
abstract::Cisplatin, a platinating agent commonly used to treat several cancers, is associated with nephrotoxicity, neurotoxicity, and ototoxicity, which has hindered its utility. To gain a better understanding of the genetic variants associated with cisplatin-induced toxicity, we present a stepwise approach integrating genotyp...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/519850
更新日期:2007-09-01 00:00:00
abstract::Although psoriasis is strongly associated with certain human leukocyte antigens (HLAs), evidence for linkage to HLA markers has been limited. The objectives of this study were (1) to provide more definitive evidence for linkage of psoriasis to HLA markers in multiplex families; (2) to compare the major HLA risk allele...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301899
更新日期:1998-07-01 00:00:00
abstract::Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2015.12.016
更新日期:2016-02-04 00:00:00
abstract::Mastocytosis is a rare myeloid neoplasm characterized by uncontrolled expansion of mast cells, driven in >80% of affected individuals by acquisition of the KIT D816V mutation. To explore the hypothesis that inherited variation predisposes to mastocytosis, we performed a two-stage genome-wide association study, analyzi...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.12.007
更新日期:2021-01-04 00:00:00
abstract::Variant late infantile neuronal ceroid lipofuscinosis (vLINCL) is an autosomal recessive progressive encephalopathy of childhood enriched in the western part of Finland, with a local incidence of 1 in 1500. We recently assigned the locus for vLINCL, CLN5, to 13q21.1-q32. In the present study, the haplotype analysis of...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::Idiopathic torsion dystonia (ITD) is characterized by involuntary twisting movements and postures. A gene for this disorder, DYT1, was mapped to chromosome 9q34 in 12 Ashkenazi Jewish (AJ) families and one large non-Jewish kindred. In the AJ population, strong linkage disequilibrium exists between DYT1 and adjacent ma...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::There is an inverse relationship between serum bilirubin concentrations and risk of coronary artery disease. The strength of the association is similar to that of smoking, systolic blood pressure, and HDL cholesterol. We carried out a genomewide scan in a Framingham Heart Study. Our study sample consisted of 330 famil...
journal_title:American journal of human genetics
pub_type: 杂志文章,多中心研究
doi:10.1086/373964
更新日期:2003-04-01 00:00:00
abstract::Hermansky-Pudlak syndrome (HPS) is genetically heterogeneous, and mutations in seven genes have been reported to cause HPS. Autozygosity mapping studies were undertaken in a large consanguineous family with HPS. Affected individuals displayed features of incomplete oculocutaneous albinism and platelet dysfunction. Ski...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/499338
更新日期:2006-01-01 00:00:00
abstract::We have previously shown that rheumatoid arthritis (RA) risk alleles overlap between different ethnic groups. Here, we utilize a multiethnic approach to show that we can effectively discover RA risk alleles. Thirteen putatively associated SNPs that had not yet exceeded genome-wide significance (p < 5 × 10(-8)) in our ...
journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
doi:10.1016/j.ajhg.2012.01.010
更新日期:2012-03-09 00:00:00
abstract::Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). Three unrelated PH1 patients, who possess a novel complex phenotype, are described. At the enzymological level, this phenotype is character...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::To investigate the molecular basis for the distinct neuronopathic phenotypes of Gaucher disease, acid beta-glucosidases expressed from mutant DNAs in Gaucher disease type 2 (acute) and type 3 (subacute) patients were characterized in fibroblasts and with the baculovirus expression system in insect cells. Expression of...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::The distribution of HLA antigens in a sample of 124 Chagas serologically positive Chilean individuals was studied. The sample was subdivided according to the presence or absence of chagasic cardiomyopathy, in order to search for genetic differences associated with this pathological condition. The frequency of antigen ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-11-01 00:00:00
abstract::Mutations in the MCOLN1 gene cause mucolipidosis type IV (MLIV), a severely debilitating, autosomal recessive, lysosomal storage disorder. Approximately 80% of patients with MLIV are of Ashkenazi Jewish (AJ) descent, and two mutations, IVS3-2A-->G and 511del6434, account for >95% of the mutant alleles in this populati...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/339519
更新日期:2002-04-01 00:00:00
abstract::New information has been obtained on 30 patients with isolated persistent hypermethioninemia, most of them previously unreported. Biopsies to confirm the presumptive diagnosis of partially deficient activity of ATP: L-methionine S-adenosyltransferase (MAT; E.C.2.5.1.6) in liver were not performed on most of these pati...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.10.002
更新日期:2008-11-01 00:00:00
abstract::When population geneticists wish to determine the genetic consequences of some aspect of mating behavior, it is often necessary to compare observed levels of consanguinity to the level expected when mating is random with respect to the factor being studied. Expectations under random mating are often derived from discr...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::Although type IV glycogen storage disease (Andersen disease; McKusick 23250) is considered to be a rare, autosomally recessive disorder, of the more than 600 patients with glycogenosis identified in our laboratory by enzymatic assays, 6% have been shown to be deficient in the glycogen branching enzyme. Most of the 38 ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::We describe a new user-intense-learning experience that incorporates the teaching of clinical and research applications of human genetics in biochemistry while training first-year medical students to develop skills in computer access to the literature. Human genetics was incorporated into the biochemistry curriculum b...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::The genetic locus for facioscapulohumeral muscular dystrophy (FSHD) has been mapped to chromosome 4. We have examined linkage to five chromosome 4q DNA markers in 22 multigenerational FSHD families. Multipoint linkage analyses of the segregation of four markers in the FSHD families and in 40 multigenerational mapping ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::Disordered mitochondrial metabolism may play an important role in a number of idiopathic neurodegenerative disorders. The question of mitochondrial dysfunction is particularly attractive in the case of idiopathic Parkinson disease (PD), since Vyas et al. recognized in the 1980s that the parkinsonism-inducing compound ...
journal_title:American journal of human genetics
pub_type: 杂志文章,评审
doi:10.1086/301812
更新日期:1998-04-01 00:00:00
abstract::A convenient and reliable method for simulatneous visualization of silver staining (Ag-NOR) of the nucleolus organizers and fluorescent bandings in metaphase chromosomes is described. Studies employing this combined procedure on human chromosomes revealed that the Ag-NOR patterns may be characteristic for each chromos...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00