Abstract：
:Linkage analysis of phenylketonurics has shown a strong association between the DNA haplotype at the phenylalanine hydroxylase (PAH) locus and phenylketonuria (PKU). Similarly, a genetic linkage between less severe forms of hyperphenylalaninemia (HPA) and the PAH locus has been suggested. In the present study we analyzed this linkage in more detail. Haplotypes at the PAH locus were determined for 19 individuals with moderately elevated plasma phenylalanine and normal urinary neopterin/biopterin ratios. Fourteen of these individuals had plasma phenylalanine levels of 4-10 mg/dl (mild HPA), and the other five had plasma phenylalanine levels of 10-19 mg/dl (atypical PKU). Thirteen of the 15 HPA families consisted of an affected child and at least one other sibling. Elevated plasma phenylalanine was seen to genetically segregate with specific PAH alleles in each family. Summation of the LOD scores for both categories of moderate plasma phenylalanine elevation gave a maximum value of 3.556 at theta = 0. At theta = 0 this gives a probability of linkage between the PAH locus and the locus for moderate phenylalanine elevations that is approximately 3,600:1. None of the alleles segregating with either mild HPA or atypical PKU were of haplotype 2 or 3, and 13/20 were of types 1 or 4. This is in agreement with the most deleterious mutations being on haplotypes 2 and 3 and with the less severe mutations being on haplotypes 1 and 4. chi 2 Analyses indicated no statistically significant correlation between HPA and a particular haplotype or restriction-enzyme site.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Di Silvestre D,Pandya A,Koch R,Groffen Jsubject
Has Abstractpub_date
1990-10-01 00:00:00pages
706-11issue
4eissn
0002-9297issn
1537-6605journal_volume
47pub_type
杂志文章abstract：:Cloned genomic DNA sequences corresponding to various regions of the human type II procollagen gene were used to analyze the DNA from 78 normal volunteers. Southern hybridization experiments detected polymorphic HindIII, BamHI, and EcoRI sites. The presence of the polymorphic HindIII site results in a 7.0-kilobase (kb...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group of neurodegenerative disorders, has been mapped to chromosome 14q32.1. ADCA type I patients from families segregating SCA3 share clinical features in common with tho...
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：: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：:The ascertainment problem arises when families are sampled by a nonrandom process and some assumption about this sampling process must be made in order to estimate genetic parameters. Under classical ascertainment assumptions, estimation of genetic parameters cannot be separated from estimation of the parameters of th...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:Increasing public interest in direct-to-consumer (DTC) genetic ancestry testing has been accompanied by growing concern about issues ranging from the personal and societal implications of the testing to the scientific validity of ancestry inference. The very concept of "ancestry" is subject to misunderstanding in both...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.03.011
更新日期：2010-05-14 00:00:00
abstract：:We report the results of biochemical and molecular investigations on a group of patients from the Saguenay-Lac-Saint-Jean region of Quebec who have an unusual form of cytochrome oxidase deficiency and Leigh disease. This group can be distinguished from the classical presentation of cytochrome oxidase deficiency with L...
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：:Estimation of recombination fractions and interference coefficients is of importance in multilocus linkage analysis. With the development of molecular genetic technologies such as RFLP, multilocus data are readily available to researchers. Several methods have been developed to analyze such data, and each performs wel...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：:We have previously shown that a quantitative-trait locus linked to the OCA2 region of 15q accounts for 74% of variation in human eye color. We conducted additional genotyping to clarify the role of the OCA2 locus in the inheritance of eye color and other pigmentary traits associated with skin-cancer risk in white popu...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/510885
更新日期：2007-02-01 00:00:00
abstract：:Catecholamine-induced polymorphic ventricular tachycardia (PVT) is characterized by episodes of syncope, seizures, or sudden death, in response to physical activity or emotional stress. Two modes of inheritance have been described: autosomal dominant and autosomal recessive. Mutations in the ryanodine receptor 2 gene ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/324565
更新日期：2001-12-01 00:00:00
abstract：:The genetically inactive, late-replicating human female X chromosome can be effectively distinguished from its more active, earlier-replicating homologue, when cells are grown according to the appropriate BrdU-33258 Hoechst protocol. Results obtained from a fluorescence analysis of DNA replication in X chromosomes are...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
abstract：:A novel technique for detecting electrophoretic and quantitative variants of group-specific component (Gc) proteins is described. The technique, in vitro labeling with radioactive vitamin D followed by polyacrylamide gel electrophoresis and autoradiography (PAGE autoradiography), permits sensitive, high resolution det...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1977-11-01 00:00:00
abstract：:Central core disease (CCO) is an autosomal dominant myopathy clinically distinct from malignant hyperthermia (MHS). In a large kindred in which the gene for CCO is segregating, two-point linkage analysis gave a maximum lod score, between the central core disease locus (CCO) and the ryanodine receptor locus (RYR1), of ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:Pregnancy-induced hypertension may be regarded as a manifestation of endothelial-cell dysfunction. The role of the eNOS gene in the development of a familial pregnancy-induced hypertension was evaluated by analysis of linkage among affected sisters and in multiplex families (n = 50). Markers from a 4-cM region encodin...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/514843
更新日期：1997-08-01 00:00:00
abstract：:Both sequence variation and copy-number variation (CNV) of the genes encoding receptors for immunoglobulin G (Fcγ receptors) have been genetically and functionally associated with a number of autoimmune diseases. However, the molecular nature and evolutionary context of this variation is unknown. Here, we describe the...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.04.018
更新日期：2012-06-08 00:00:00
abstract：:A novel type IV collagen, alpha 3(IV), has recently been identified in human and bovine basement membranes. Here we describe the cloning and sequencing of a cDNA encoding 218 residues of the NC1 domain of the human alpha 3(IV) chain. Of interest is the possible role of abnormalities of the alpha 3(IV) chain in Alport ...
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：:Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.11.020
更新日期：2014-01-02 00:00:00
abstract：:In studies of expression quantitative trait loci (eQTLs), it is of increasing interest to identify eGenes, the genes whose expression levels are associated with variation at a particular genetic variant. Detecting eGenes is important for follow-up analyses and prioritization because genes are the main entities in biol...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2015.04.012
更新日期：2015-06-04 00:00:00
abstract：:Timely molecular diagnosis of RB1 mutations enables earlier treatment, lower risk, and better health outcomes for patients with retinoblastoma; empowers families to make informed family-planning decisions; and costs less than conventional surveillance. However, complexity has hindered clinical implementation of molecu...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/345651
更新日期：2003-02-01 00:00:00
abstract：:X-linked adrenoleukodystrophy (ALD), a neurodegenerative disorder associated with impaired beta-oxidation of very-long-chain fatty acids (VLCFA), is due to mutations in a gene encoding a peroxisomal ATP-binding cassette (ABC) transporter (ALD protein [ALDP]). We analyzed the open reading frame of the ALD gene in 44 Fr...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotyp...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:Experiments designed to illuminate the mechanism by which folic acid and thymidine inhibit expression of the Xq28 fragile site in human lymphocytes are described. The fragile site is induced by 5-fluorodeoxyuridine (FUdR), a potent inhibitor of thymidylate synthetase, in the presence of otherwise inhibiting concentrat...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:Inhibition of replicative DNA synthesis following gamma-irradiation is observed in eukaryotic cells but is defective in cells derived from patients with the cancer-prone inherited disorder ataxia-telangiectasia (A-T) and in A-T-like Chinese hamster cell mutants. Chinese hamster cells show a less pronounced inhibition ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:Heteroplasmy, the existence of multiple mtDNA types within an individual, has been previously detected by using mostly indirect methods and focusing largely on just the hypervariable segments of the control region. Next-generation sequencing technologies should enable studies of heteroplasmy across the entire mtDNA ge...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.07.014
更新日期：2010-08-13 00:00:00
abstract：:Distal hereditary motor neuropathies comprise a clinically and genetically heterogeneous group of disorders. We recently mapped an X-linked form of this condition to chromosome Xq13.1-q21 in two large unrelated families. The region of genetic linkage included ATP7A, which encodes a copper-transporting P-type ATPase mu...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.01.027
更新日期：2010-03-12 00:00:00
abstract：:Previously, we demonstrated evidence of linkage to bipolar affective disorder (BP) in a single large, multigenerational family with a LOD score of 3.41 at the PFKL locus on chromosome 21q22.3. Additional families showed little support for linkage to PFKL under homogeneity or heterogeneity, in that study. We have expan...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302185
更新日期：1999-01-01 00:00:00
abstract：:Deletions of the long arm of chromosome 18 occur in approximately 1 in 10,000 live births. Congenital aural atresia (CAA), or narrow external auditory canals, occurs in approximately 66% of all patients who have a terminal deletion 18q. The present report describes a series of 20 patients with CAA, of whom 18 had micr...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/375695
更新日期：2003-06-01 00:00:00
abstract：:Primary hyperoxaluria (PH) is an autosomal-recessive disorder of endogenous oxalate synthesis characterized by accumulation of calcium oxalate primarily in the kidney. Deficiencies of alanine-glyoxylate aminotransferase (AGT) or glyoxylate reductase (GRHPR) are the two known causes of the disease (PH I and II, respect...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.07.023
更新日期：2010-09-10 00:00:00
abstract：:Germline mutations of PTEN (phosphatase and tensin homolog deleted on chromosome 10) are associated with the multihamartomatous disorder Cowden syndrome (CS). Moreover, patients with CS with germline PTEN promoter mutations have aberrant PTEN protein expression and an increased frequency of breast cancer. Here, we exa...
journal_title：American journal of human genetics
pub_type： 杂志文章,多中心研究
doi：10.1086/521051
更新日期：2007-10-01 00:00:00
abstract：:Huntington disease (HD) is a dominantly inherited neurodegenerative disorder characterized by dysregulation of various genes. Recently, microRNAs (miRNAs) have been reported to be involved in this dysregulation, suggesting that manipulation of appropriate miRNA regulation may have a therapeutic benefit. Here, we repor...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.05.025
更新日期：2013-08-08 00:00:00
abstract：:To identify Chinese geneticists' views of ethical issues in genetic testing and screening, a national survey was conducted. Of 402 Chinese geneticists asked to participate, 255 (63%) returned by mail anonymous questionnaires. The majority of respondents thought that genetic testing should be offered in the workplace f...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302020
更新日期：1998-09-01 00:00:00
