Abstract：
:Dermal fibroblasts from most individuals with osteogenesis imperfecta (OI) type I produce about half the normal amount of type I procollagen, as a result of decreased synthesis of one of its constituent chains, pro alpha 1 (I). To test the hypothesis that decreased synthesis of pro alpha (I) chains results from mutations in the COL1A1 gene, we used primer extension with nucleotide-specific chain termination to measure the contribution of individual COL1A1 alleles to the mRNA pool in fibroblasts from affected individuals. A polymorphic MnlI restriction endonuclease site in the 3'-untranslated region of COL1A1 was used to distinguish the transcripts of the two alleles in heterozygous individuals. Twenty-three individuals from 21 unrelated families were studied. In each case there was marked diminution in steady-state mRNA levels from one COL1A1 allele. Loss of an allele through deletion or rearrangement was not the cause of the diminished COL1A1 mRNA levels. Primer extension with nucleotide-specific chain termination allows identification of the mutant COL1A1 allele in cell strains that are heterozygous for an expressed polymorphism. It is applicable to sporadic cases, to small families, and to large families in whom key individuals are uninformative at the polymorphic sites used in linkage analysis, making it a useful adjunct to the biochemical screening of collagenous proteins for OI.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Willing MC,Pruchno CJ,Atkinson M,Byers PHsubject
Has Abstractpub_date
1992-09-01 00:00:00pages
508-15issue
3eissn
0002-9297issn
1537-6605journal_volume
51pub_type
杂志文章abstract：:A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide sc...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/423900
更新日期：2004-09-01 00:00:00
abstract：:Seventy-seven Ethiopians were investigated for mtDNA and Y chromosome-specific variations, in order to (1) define the different maternal and paternal components of the Ethiopian gene pool, (2) infer the origins of these maternal and paternal lineages and estimate their relative contributions, and (3) obtain informatio...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301702
更新日期：1998-02-01 00:00:00
abstract：:Helicobacter pylori is considered the most prevalent infectious agent among humans, and it causes gastric inflammation, gastroduodenal ulcers, and a risk of gastric cancer. We performed a genomewide linkage analysis among Senegalese siblings phenotyped for H. pylori-reactive serum immunoglobulin G. A multipoint LOD sc...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/367714
更新日期：2003-02-01 00:00:00
abstract：:Familial juvenile polyposis (FJP) is a hamartomatouspolyposis syndrome in which affected family members develop upper and lower gastrointestinal juvenile polyps and are at increased risk for gastrointestinal cancer. A genetic locus for FJP has not yet been identified by linkage; therefore, the objective of this study ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301840
更新日期：1998-05-01 00:00:00
abstract：:Elsewhere we have reported an efficient method for isolating VNTR (Variable Number of Tandem Repeats) markers. Several of the VNTR markers isolated in those experiments were sequenced, and a DNA sequence of 9 bp (GNNGTGGG) emerged as an apparent consensus sequence for VNTR markers. To confirm this result and to develo...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:We devised a rapid PCR-based method to screen for an A----G transition at nucleotide 8344 of the human mitochondrial tRNA(Lys) gene, which was recently reported, by Shoffner and co-workers, to be associated with myoclonus epilepsy and ragged-red fibers (MERRF), a maternally transmitted mitochondrial encephalomyopathy ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
abstract：:Recently the second gene for autosomal dominant polycystic kidney disease (ADPKD), located on chromosome 4q21-q22, has been cloned and characterized. The gene encodes an integral membrane protein, polycystin-2, that shows amino acid similarity to the PKD1 gene product and to the family of voltage-activated calcium (an...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/515497
更新日期：1997-09-01 00:00:00
abstract：:The still debated question of whether the expression of mental retardation in heterozygous carriers of the Martin-Bell syndrome is influenced by X inactivation has been investigated in a group of phase-known double heterozygotes for the FRA-X mutant and the G6PD Mediterranean variant. In these individuals, the number ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:In this paper we present linkage results from the analysis of 18 Utah breast cancer kindreds, for three 17q markers. Four kindreds had LOD scores greater than 1.0 for at least one of the marker loci. One of these kindreds has a LOD score of 6.07 with D17S579, and we believe it to be the most informative 17q family rep...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:Hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder belonging to a group of muscle diseases involving the abnormal function of ion channels. This group of muscle diseases also comprises hyperkalemic periodic paralysis and paramyotonia congenita, both sodium-channel diseases, and myotonia congenit...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-02-01 00:00:00
abstract：:The etiology of acquired partial lipodystrophy (APL, also called "Barraquer-Simons syndrome") is unknown. Genomic DNA mutations affecting the nuclear lamina protein lamin A cause inherited partial lipodystrophy but are not found in patients with APL. Because it also encodes a nuclear lamina protein (lamin B2) and its ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/505885
更新日期：2006-08-01 00:00:00
abstract：:We tested 519 chromosome 3-specific cosmids for the presence of rare restriction-endonuclease sites in a search for cosmids containing HTF islands. We have identified 49 cosmids (9% of those tested) that contain multiple rare restriction-endonuclease sites. The cosmids were digested with several common cutting restric...
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：:An expanded G4C2 repeat in C9orf72 represents the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the lower limit for pathological expansions is unknown (the suggested cutoff is 30 repeats). It has been proposed that the expansion might have...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2015.04.016
更新日期：2015-06-04 00:00:00
abstract：:The Huntington disease (HD) gene has been mapped to the most distal subband of chromosome 4p. Analysis of recombination events has not provided an unequivocal location of the HD gene, but it indicates a position very close to the telomere as one possibility. We have constructed a yeast artificial chromosome (YAC) vect...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:The recent cloning of cDNA encoding the Ca++ release channel (ryanodine receptor) of human sarcoplasmic reticulum has enabled us to use somatic cell hybrids to localize the ryanodine receptor gene (RYR) to the proximal long arm of human chromosome 19. Studies with additional hybrids containing deletions or translocati...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：:We explored the biochemical basis for the disorder pseudohypophosphatasia (PsHYPT) in one patient by examining the substrate specificity and localization of alkaline phosphatase (ALP) in cultured dermal fibroblasts. Despite substantial ALP activity, in cell homogenates, toward the artificial substrate 4-methyl-umbelli...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:A stepwise logistic-regression procedure is proposed for evaluation of the relative importance of variants at different sites within a small genetic region. By fitting statistical models with main effects, rather than modeling the full haplotype effects, we generate tests, with few degrees of freedom, that are likely ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/338007
更新日期：2002-01-01 00:00:00
abstract：:Eighty unrelated individuals with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) were found to have deletions in the major deletion-rich region of the DMD locus. This region includes the last five exons detected by cDNA5b-7, all exons detected by cDNA8, and the first two exons detected by cDNA9. ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:Gyrate atrophy of the choroid and retina that is due to ornithine ketoacid transaminase (OKT) deficiency is an autosomal recessive disorder. Fibroblasts from heterozygotes for the pyridoxine-responsive variant as well as those for the pyridoxine-nonresponsive variant contain intermediate levels of OKT activity. These ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:The fourth-year medical student elective in clinical genetics has been enhanced by the addition of a problem-solving project. The assignment requires students to pose and answer a practical question about a professionally relevant genetic problem. Exemplary questions and the details of the exercise are given. Six of 1...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Spinal muscular atrophy is a neurodegenerative disorder caused by the deletion or mutation of the survival-of-motor-neuron gene, SMN1. An SMN1 paralog, SMN2, differs by a C-->T transition in exon 7 that causes substantial skipping of this exon, such that SMN2 expresses only low levels of functional protein. A better u...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/498853
更新日期：2006-01-01 00:00:00
abstract：:The Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect biosamples with consent from at least one million veterans. Presently, blood samples have been collected from over 800,000 enrolled participants. The size and diversity of the MVP cohort, as well as the availabilit...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2020.03.004
更新日期：2020-04-02 00:00:00
abstract：:The association between normal alleles at the CTG repeat and two nearby polymorphisms in the myotonin protein kinase gene, the Alu insertion/deletion polymorphism and the myotonic dystrophy kinase (DMK)(G/T) intron 9/HinfI polymorphism, has been analyzed in South African Negroids, a population in which myotonic dystro...
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：:GWAS have been successful in identifying disease susceptibility loci, but it remains a challenge to pinpoint the causal variants in subsequent fine-mapping studies. A conventional fine-mapping effort starts by sequencing dozens of randomly selected samples at susceptibility loci to discover candidate variants, which a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.04.003
更新日期：2010-05-14 00:00:00
abstract：:The polymerase chain reaction (PCR) makes it possible to rapidly generate a very large number of copies of a specific region of DNA. Application of PCR to individual human sperm cells permits the typing of a large number of independent male meiotic events. If the donor male is heterozygous at three loci, sperm typing ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:We examined DNA polymorphisms in the nonrecombining portion of the Y-chromosome to investigate the contribution of distinct patrilineages to the present-day white Brazilian population. Twelve unique-event polymorphisms were typed in 200 unrelated males from four geographical regions of Brazil and in 93 Portuguese male...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/316931
更新日期：2001-01-01 00:00:00
abstract：:Juvenile hemochromatosis (JH) is an autosomal recessive disorder that leads to severe iron loading in the 2d to 3d decade of life. Affected members in families with JH do not show linkage to chromosome 6p and do not have mutations in the HFE gene that lead to the common hereditary hemochromatosis. In this study we per...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302379
更新日期：1999-05-01 00:00:00
abstract：:To investigate the molecular basis of phenylketonuria in Italy we applied the chemical cleavage method (CCM) on amplified DNA encompassing exons 7 and 8 of the phenylalanine hydroxylase gene. These exons are in a region likely to be involved in enzyme function. Using this approach, we could simultaneously screen for n...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:Fragile X premutations are considered to be a risk factor for premature ovarian failure (POF), which is usually defined as menopause at age <40 years. Since premutations may be inherited from either the mother or the father, we evaluated the influence of the inheritance pattern on the duration of reproductive life in ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302774
更新日期：2000-02-01 00:00:00
abstract：:Autosomal-recessive congenital ichthyoses represent a large and heterogeneous group of disorders of epidermal cornification. Recent data suggest that most of these disorders might result from defective lipid transport and metabolism. In the present study, we describe a late-onset form of recessive ichthyosis in a larg...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2011.02.011
更新日期：2011-04-08 00:00:00
