Abstract：
:A survey of Wilson disease in Iceland has revealed two large kindreds with affected individuals. We have carried out studies of haplotypes of dinucleotide repeat polymorphisms (CA repeats) flanking the Wilson disease gene. The same mutation, a 7-bp deletion, is present in both families, and the clinical features are similar. The haplotype data and nature of the mutation support the existence of a founder chromosome carrying the mutation. This Icelandic mutation was not found in patients of Irish or Scottish origins, who could share some of the Icelandic ancestral genes. Although the protein function is predicted to be completely abolished by the deletion, predicting early-onset liver disease, we find that the patients present with later-onset neurological and psychiatric symptoms. We show that alternative splicing of the transcript in the region of the deletion could contribute to later onset, suggesting that alternative isoforms of the protein might have some functional significance.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Thomas GR,Jensson O,Gudmundsson G,Thorsteinsson L,Cox DWsubject
Has Abstractpub_date
1995-05-01 00:00:00pages
1140-6issue
5eissn
0002-9297issn
1537-6605journal_volume
56pub_type
杂志文章abstract：:The results of an empirical nucleotide-sequencing approach indicate that the evolution of the human mitochondrial noncoding D-loop is both more rapid and more complex than is revealed by standard phylogenetic approaches. The nucleotide sequence of the D-loop region of the mitochondrial genome was determined for 45 mem...
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：:X inactivation involves initiation, propagation, and maintenance of genetic inactivation. Studies of replication timing in X;autosome translocations have suggested that X inactivation may spread into adjacent autosomal DNA. To examine the inactivation of autosomal material at the molecular level, we assessed the trans...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301922
更新日期：1998-07-01 00:00:00
abstract：:Pc 1 Duarte is a mutant brain protein present in 32% of the normal human population with 2.6% being homozygous. Preliminary studies suggest an increased frequency of this mutation in individuals with affective disease. To determine if this mutant was present in primates, 32 fetal (wild)-born baboons were examined. All...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1981-01-01 00:00:00
abstract：:We present a systematic review of pleiotropy among SNPs and genes reported to show genome-wide association with common complex diseases and traits. We find abundant evidence of pleiotropy; 233 (16.9%) genes and 77 (4.6%) SNPs show pleiotropic effects. SNP pleiotropic status was associated with gene location (p = 0.024...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1016/j.ajhg.2011.10.004
更新日期：2011-11-11 00:00:00
abstract：:Eleven normal families with at least four children were studied cytogenetically using the C-band technique to identify polymorphisms in the constitutive heterochromatin of chromosomes 1, 9 and 16. Thirteen individuals showed one or more variants in such chromosomes. The analysis of the segregation ratios in the 35 off...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1976-07-01 00:00:00
abstract：:Genomic rearrangements involving the peripheral myelin protein gene (PMP22) in human chromosome 17p12 are associated with neuropathy: duplications cause Charcot-Marie-Tooth disease type 1A (CMT1A), whereas deletions lead to hereditary neuropathy with liability to pressure palsies (HNPP). Our previous studies showed th...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.05.001
更新日期：2010-06-11 00:00:00
abstract：:Escobar syndrome is a form of arthrogryposis multiplex congenita and features joint contractures, pterygia, and respiratory distress. Similar findings occur in newborns exposed to nicotinergic acetylcholine receptor (AChR) antibodies from myasthenic mothers. We performed linkage studies in families with Escobar syndro...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/506257
更新日期：2006-08-01 00:00:00
abstract：:Two new morphs (F and G) detected by the centromeric alpha satellite probe p alpha 10RP8 and D10Z1 in HinfI digests are linked to the PstI polymorphisms of D10Z1, confirming their chromosome 10 location. The F and G morphs were in strong linkage disequilibrium with each other but were in weak linkage disequilibrium wi...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:The association between HLA-DR and -DQ and insulin-dependent diabetes mellitus (IDDM) in a defined high-incidence area was analyzed in a total of 58 population-based patients, representing 77% of IDDM patients with age at onset below 16 years, and in 92 unrelated parents in control families without IDDM. HLA haplotype...
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：:Deletions of the distal short arm of chromosome 1 (1p36) represent a common, newly delineated deletion syndrome, characterized by moderate to severe psychomotor retardation, seizures, growth delay, and dysmorphic features. Previous cytogenetic underascertainment of this chromosomal deletion has made it difficult to ch...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/515520
更新日期：1997-09-01 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：:The putative locus for hereditary mixed polyposis syndrome (HMPS) in a large family of Ashkenazi descent (SM96) was previously reported to map to chromosome sub-bands 6q16-q21. However, new clinical data, together with molecular data from additional family members, have shown 6q linkage to be incorrect. A high-density...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/375144
更新日期：2003-05-01 00:00:00
abstract：:The microsatellite marker DXS426 maps to the interval Xp21.1-Xp11.21, the chromosomal region which contains two loci for X-linked retinitis pigmentosa (XLRP; RP2 and RP3). We have refined the localization of DXS426 both physically, by mapping it to a deletion which spans the interval Xp21.3-Xp11.23, and genetically, b...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:The pheochromocytomas are an important cause of secondary hypertension. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of nonsyndromic familial pheochromocytoma is unknown. Rece...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/321282
更新日期：2001-07-01 00:00:00
abstract：:We have evaluated eight patients with pigmentary anomalies reminiscent of incontinentia pigmenti or hypomelanosis of Ito. All demonstrated abnormal lymphocyte karyotypes with chromosomal mosaicism in lymphocytes and/or skin fibroblasts. In seven the skin was darkly pigmented, and in all of these seven cases the abnorm...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：
更新日期：1989-08-01 00:00:00
abstract：:Supernumerary marker chromosomes (SMCs) of chromosome 15, designated "SMC(15)s," are the most common SMC in humans, accounting for as much as 60% of all those observed. We report the characterization of 46 large SMC(15)s, using both fluorescence in situ hybridization and polymerase chain reaction analysis within and d...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/379155
更新日期：2003-11-01 00:00:00
abstract：:Hypotrichosis simplex (HS) comprises a group of hereditary isolated alopecias that are characterized by a diffuse and progressive loss of hair starting in childhood and shows a wide phenotypic variability. We mapped an autosomal-dominant form of HS to chromosome 1q31.3-1q41 in a Spanish family. By direct sequencing, w...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.10.022
更新日期：2013-01-10 00:00:00
abstract：:The homodimeric transmembrane receptor natriuretic peptide receptor B (NPR-B [also known as guanylate cyclase B, GC-B, and GUC2B]; gene name NPR2) produces cytoplasmic cyclic GMP from GTP on binding its extracellular ligand, C-type natriuretic peptide (CNP). CNP has previously been implicated in the regulation of skel...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/422013
更新日期：2004-07-01 00:00:00
abstract：:Nine markers from the pericentromeric region of chromosome 17 were typed in 16 British and five South African families with neurofibromatosis type 1 (NF1). The markers--p17H8, pHHH202, and EW204--were linked to NF1 at recombination fractions less than 1%. No evidence of locus heterogeneity was detected. Inspection of ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：:Attention-deficit hyperactivity disorder (ADHD) affects approximately 3%-5% of children in the United States. In the current psychiatric nomenclature, ADHD comprises three subtypes: inattentive, hyperactive-impulsive, and combined. In this study, we used four analytic strategies to examine the association and linkage ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302132
更新日期：1998-12-01 00:00:00
abstract：:Recent advances in genome technology have led to mapping and subsequent isolation, by positional cloning, of a number of genes for common and/or complex human diseases. It therefore will be possible to utilize information about a known locus in the search for additional, perhaps less penetrant, genes for a particular ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1997-05-01 00:00:00
abstract：:Samples of venous blood from 239 male and 476 female adults including 41 pairs of parents and 123 of their children belonging to a Surinam population called the Djuka or Bush Negroes of West African origin were screened for electrophoretic variants of red cell glutathione peroxidase (GPX1) in Cellogel. The results con...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-05-01 00:00:00
abstract：:In linkage analysis, when the lod score is maximized over multiple genetic models, standard asymptotic approximation of the significance level does not apply. Monte Carlo methods can be used to estimate the p value, but procedures currently used are extremely inefficient. We propose a Monte Carlo procedure based on th...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-12-01 00:00:00
abstract：:Knowledge of the number of causative loci is necessary to estimate the power of mapping studies of complex diseases. In the present article, we reexamine a theory developed by Risch and its implications for estimating the number L of causative loci affecting a complex inherited disease. We first show that methods base...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/344779
更新日期：2002-12-01 00:00:00
abstract：:We have investigated the molecular basis for HbH disease in 16 patients from Sardinia, and central and southern Italy. We have shown that HbH disease is produced by the interaction of at least 10 different deletional or nondeletional alpha-thalassemia haplotypes, some of which have been already described in the Medite...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-11-01 00:00:00
abstract：:Down syndrome is a complex genetic and metabolic disorder attributed to the presence of three copies of chromosome 21. The extra chromosome derives from the mother in 93% of cases and is due to abnormal chromosome segregation during meiosis (nondisjunction). Except for advanced age at conception, maternal risk factors...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/303055
更新日期：2000-09-01 00:00:00
abstract：:Genes comprising the major histocompatibility complex (MHC) play a central role in governing the immune response of vertebrates. A great deal of information has been revealed on the molecular biology and physiology of these loci, but three features-the high polymorphism, tight linkage among the loci, and the nonrandom...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:Cerebral cavernous malformations (CCM) are hamartomatous vascular malformations characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. They cause seizures and focal neurological deficits due to cerebral hemorrhages. CCM loci have already been assigned to chromosomes 7q (CCM1), 7p...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/381718
更新日期：2004-02-01 00:00:00
abstract：:The alkaline phosphatases comprise a multigene enzyme family that hydolyze phosphate esters and are widely distributed in nature. Three main classes have been isolated from humans, the placental, intestinal, and liver/bone/kidney forms. We have mapped the placental and intestinal alkaline phosphatase genes to 2q34-q37...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:Whether smoking-associated DNA methylation has a causal effect on lung function has not been thoroughly evaluated. We first investigated the causal effects of 474 smoking-associated CpGs on forced expiratory volume in 1 s (FEV1) in UK Biobank (n = 321,047) by using two-sample Mendelian randomization (MR) and then repl...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2020.01.015
更新日期：2020-03-05 00:00:00
