Abstract：
:Phenylketonuria (PKU), a disorder of amino acid metabolism prevalent among Caucasians and other ethnic groups, is caused primarily by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). PKU is a highly heterogeneous disorder, with more than 60 molecular lesions identified in the PAH gene. The haplotype associations, relative frequencies, and distributions of five prevalent PAH mutations (R158Q, R261Q, IVS10nt546, R408W, and IVS12n1) were established in a comprehensive European sample population and subsequently were examined to determine the potential roles of several genetic mechanisms in explaining the present distribution of the major PKU alleles. Each of these five mutations was strongly associated with only one of the more than 70 chromosomal haplotypes defined by eight RFLPs in or near the PAH gene. These findings suggest that each of these mutations arose through a single founding event that occurred within time periods ranging from several hundred to several thousand years ago. From the significant differences observed in the relative frequencies and distributions of these five alleles throughout Europe, four of these putative founding events could be localized to specific ethnic subgroups. Together, these data suggest that there were multiple, geographically and ethnically distinct origins for PKU within the European population.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Eisensmith RC,Okano Y,Dasovich M,Wang T,Güttler F,Lou H,Guldberg P,Lichter-Konecki U,Konecki DS,Svensson Esubject
Has Abstract,Author List Incompletepub_date
1992-12-01 00:00:00pages
1355-65issue
6eissn
0002-9297issn
1537-6605journal_volume
51pub_type
杂志文章abstract：:The reported linkage between cutaneous melanoma and the dysplastic nevus syndrome (CM/DNS) to markers located on the distal portion of the short arm of chromosome 1 was examined in three Utah kindreds ascertained for multiple cases of melanoma. Family members in these kindreds were genotyped for the two markers report...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-05-01 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：:The gene has been proposed as an attractive unit of analysis for association studies, but a simple yet valid, powerful, and sufficiently fast method of evaluating the statistical significance of all genes in large, genome-wide datasets has been lacking. Here we propose the use of an extended Simes test that integrates...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2011.01.019
更新日期：2011-03-11 00:00:00
abstract：:To better define the nature of FMR1 CGG-repeat expansions, changes in allele sizes for 191 families with fragile X and for 33 families with gray-zone repeats (40-60) were analyzed. Expansion of the fragile X chromosome to the full mutation was seen in 13.4% of offspring from premutation mothers with 56-59 repeats, 20....
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:A gene for Holt-Oram syndrome (HOS) has been previously mapped to chromosome 12q2 and designated HOS1. We have identified a HOS patient with a de novo chromosomal rearrangement involving 12q. Detailed cytogenetic analysis of this case reveals three breaks on 12q, and two of these are within the HOS1 interval. By using...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:A family with three children with trisomy 21 in which the mother is a phenotypically normal, trisomy 21/normal mosaic was studied. Chromosome 21 fluorescent heteromorphisms were used to document that two of the three number 21's in two of the Down syndrome offspring were of maternal origin. Five cytogenetic surveys in...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1982-01-01 00:00:00
abstract：:The parental origin of the supernumerary chromosome 18 was investigated by RFLP analysis in 23 individuals with Edwards syndrome. All families were studied with the DNA probe pERT-25, which recognizes a locus of highly polymorphic tandemly repeated DNA sequences on chromosome 18. The extra chromosome was found to be o...
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：:Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, loca...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:Ehlers-Danlos syndrome (EDS) type IV is a dominantly inherited disorder that results from mutations in the type III collagen gene (COL3A1). We studied the structure of the COL3A1 gene of an individual with EDS type IV and that of her phenotypically normal parents. The proband was heterozygous for a 2-kb deletion in CO...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-07-01 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：:EXTL3 regulates the biosynthesis of heparan sulfate (HS), important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs). By whole-exome sequencing, we identified homozygous missense mutations c.1382C>T, c.1537C>T, c.1970A>G, and c.2008T>G in EXTL3 in nine affected individ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2017.01.013
更新日期：2017-02-02 00:00:00
abstract：:The risk of epilepsy among individuals with intellectual disability (ID) is approximately ten times that of the general population. From a cohort of >5,000 families affected by neurodevelopmental disorders, we identified six consanguineous families harboring homozygous inactivating variants in MBOAT7, encoding lysopho...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.07.019
更新日期：2016-10-06 00:00:00
abstract：:Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders associated with hypokalemic alkalosis. This disorder typically presents as a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark of this variant is a ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301872
更新日期：1998-06-01 00:00:00
abstract：:Two female identical twins who were clinically normal were obligatory heterozygotes for X-linked deuteranomaly associated with a green-red fusion gene derived from their deuteranomalous father. On anomaloscopy, one of the twins was phenotypically deuteranomalous while the other had normal color vision. The color visio...
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：:Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases now accessible to therapy. Outside the Ashkenazi Jewish community, a high molecular diversity is observed, leaving approximately 30% of alleles undetected. Nevertheless, very few exhaustive methods have b...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301969
更新日期：1998-08-01 00:00:00
abstract：:Congenital bilateral aplasia of the vas deferens (CBAVD) was suggested to be a mild form of cystic fibrosis (CF). Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in males with CBAVD revealed that in some males CBAVD is caused by two defective CFTR alleles. The genetic basis of ...
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：:Genome-wide association studies are routinely conducted to identify genetic variants that influence complex disorders. It is well known that failure to properly account for population or pedigree structure can lead to spurious association as well as reduced power. We propose a method, ROADTRIPS, for case-control assoc...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.01.001
更新日期：2010-02-12 00:00:00
abstract：:We offered cystic fibrosis (CF) carrier testing to reproductive-age enrollees in an HMO, in order to determine factors associated with test utilization in a primarily nonpregnant population. Male and female enrollees either were mailed an invitation to have the test after attending an educational session (N = 2,713) o...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-10-01 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：:Increased male prevalence has been repeatedly reported in several neurodevelopmental disorders (NDs), leading to the concept of a "female protective model." We investigated the molecular basis of this sex-based difference in liability and demonstrated an excess of deleterious autosomal copy-number variants (CNVs) in f...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2014.02.001
更新日期：2014-03-06 00:00:00
abstract：:A collection of 1,069 human PCR-based genetic markers has been developed, and their distribution over the 22 autosomes and the X chromosome has been determined. Each marker was developed around a short-tandem-repeat DNA sequence. The majority (85%) of the markers described here were selected to contain tetranucleotide...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:Significantly larger variation between sibships within families of male MZ twins than between sibships within families of female MZ twins, indicative of maternal influences, was found for 10 of 41 dermatoglyphic fingertip variables. Of these, five were thumb-related with the effect primarily on the thumb radial and ri...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1979-05-01 00:00:00
abstract：:To investigate the transmission of Tourette syndrome (TS) and associated disorders within families, complex segregation analysis was performed on family study data obtained from 53 independently ascertained children and adolescents with TS and their 154 first-degree relatives. The results suggest that the susceptibili...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:Phenotypes are rarely consistent across genetic backgrounds and environments, but instead vary in many ways depending on allelic variants, unlinked genes, epigenetic factors, and environmental exposures. In the extreme, individuals carrying the same causal DNA sequence variant but on different backgrounds can be class...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1016/j.ajhg.2017.06.004
更新日期：2017-08-03 00:00:00
abstract：:Many ion channel genes have been associated with human genetic pain disorders. Here we report two large Chinese families with autosomal-dominant episodic pain. We performed a genome-wide linkage scan with microsatellite markers after excluding mutations in three known genes (SCN9A, SCN10A, and TRPA1) that cause simila...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.09.016
更新日期：2013-11-07 00:00:00
abstract：:Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent wi...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2014.06.006
更新日期：2014-07-03 00:00:00
abstract：:The two main phenotypes of inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--are chronic intestinal inflammatory disorders with a complex genetic background. Using a three-stage design, we performed a functional candidate-gene analysis of innate immune pathway in IBD. In phase I, we t...
journal_title：American journal of human genetics
pub_type： 杂志文章,多中心研究
doi：10.1016/j.ajhg.2008.03.016
更新日期：2008-05-01 00:00:00
abstract：:Multiprotein complexes referred to as outer dynein arms (ODAs) develop the main mechanical force to generate the ciliary and flagellar beat. ODA defects are the most common cause of primary ciliary dyskinesia (PCD), a congenital disorder of ciliary beating, characterized by recurrent infections of the upper and lower ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.06.014
更新日期：2016-08-04 00:00:00
abstract：:On the basis of accumulating evidence that obesity has a substantial genetic component, a genomewide search for linkages of DNA markers to percent body fat is ongoing in Pima Indians, a population with a very high prevalence of obesity. An initial screen of the genome (>600 markers in 874 individuals) has been complet...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:The genetic linkage of the loci for lymphocyte cytosol polypeptide with molecular weight of 64,000 (LCP1) and esterase (ESD) were examined by two-dimensional gel electrophoresis using blood from four informative families. No recombinants were observed in the four families totaling 17 children, giving a summed lod scor...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
