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 genotypes, gene expression, and sensitivity of HapMap cell lines to cisplatin. Cell lines derived from 30 trios of European descent (CEU) and 30 trios of African descent (YRI) were used to develop a preclinical model to identify genetic variants and gene expression that contribute to cisplatin-induced cytotoxicity in two different populations. Cytotoxicity was determined as cell-growth inhibition at increasing concentrations of cisplatin for 48 h. Gene expression in 176 HapMap cell lines (87 CEU and 89 YRI) was determined using the Affymetrix GeneChip Human Exon 1.0 ST Array. We identified six, two, and nine representative SNPs that contribute to cisplatin-induced cytotoxicity through their effects on 8, 2, and 16 gene expressions in the combined, Centre d'Etude du Polymorphisme Humain (CEPH), and Yoruban populations, respectively. These genetic variants contribute to 27%, 29%, and 45% of the overall variation in cell sensitivity to cisplatin in the combined, CEPH, and Yoruban populations, respectively. Our whole-genome approach can be used to elucidate the expression of quantitative trait loci contributing to a wide range of cellular phenotypes.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Huang RS,Duan S,Shukla SJ,Kistner EO,Clark TA,Chen TX,Schweitzer AC,Blume JE,Dolan MEdoi
10.1086/519850subject
Has Abstractpub_date
2007-09-01 00:00:00pages
427-37issue
3eissn
0002-9297issn
1537-6605pii
S0002-9297(07)61341-Xjournal_volume
81pub_type
杂志文章abstract：:A wide variety of mutations in the parkin gene, including exon deletions and duplications, as well as point mutations, result in autosomal recessive early-onset parkinsonism. Interestingly, several of these anomalies were found repeatedly in unrelated patients and may therefore result from recurrent, de novo mutationa...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/318791
更新日期：2001-03-01 00:00:00
abstract：:Now that the cystic fibrosis (CF) gene has been identified, direct genetic testing for this disorder is available. The current lack of precision has generated a controversy concerning whether population screening is advisable. However, there is general agreement that testing for CF carriers should be offered to CF-aff...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-08-01 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：: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...
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：:Sudden cardiac death is responsible for half of all deaths from cardiovascular disease. The analysis of the electrophysiological substrate for arrhythmias is crucial for optimal risk stratification. A prolonged T-peak-to-Tend (Tpe) interval on the electrocardiogram is an independent predictor of increased arrhythmic r...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2020.04.009
更新日期：2020-06-04 00:00:00
abstract：:The original test for the analysis of the CCG expansion at the FRAXE locus involves Southern blot analysis of HindIII digests. We show that, by using a different probe, the FRAXE mutation can be detected easily on the same EcoRI or EagI+EcoRI blots as are used for detection of FRAXA. Unexpectedly, we found that both t...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:The mode of inheritance of bipolar affective disorder (BPAD) appears complex, and non-Mendelian models of inheritance have been postulated. Two non-Mendelian phenomena, genomic imprinting and mitochondrial inheritance, may contribute to the complex inheritance pattern seen in BPAD. Both imprinting and mitochondrial in...
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：:Congenital universal muscular hypoplasia has been confused with similar diseases in the past. Evidence presented in this paper distinguishes this disorder from other phenotypically similar ones and indicates that it is inherited as an autosomal recessive disorder. ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1979-09-01 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：:Benign infantile familial convulsions is an autosomal dominant disorder characterized by nonfebrile seizures, with the first attack occurring at age 3-12 mo. It is one of the rare forms of epilepsy that are inherited as monogenic Mendelian traits, thus providing a powerful tool for mapping genes involved in epileptic ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/514877
更新日期：1997-10-01 00:00:00
abstract：:An autosomal recessive deficiency of acid alpha-glucosidase (GAA), type II glycogenosis, is genetically and clinically heterogeneous. The discovery of an enzyme-inactivating genomic deletion of exon 18 in three unrelated genetic compound patients--two infants and an adult--provided a rare opportunity to analyze the ef...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:Mutations in several genes encoding components of the SWI/SNF chromatin remodeling complex cause neurodevelopmental disorders (NDDs). Here, we report on five individuals with mutations in SMARCD1; the individuals present with developmental delay, intellectual disability, hypotonia, feeding difficulties, and small hand...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.02.001
更新日期：2019-04-04 00:00:00
abstract：:Autism is a heritable but genetically complex disorder characterized by deficits in language and in reciprocal social interactions, combined with repetitive and stereotypic behaviors. As with many genetically complex disorders, numerous genome scans reveal inconsistent results. A genome scan of 345 families from the A...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/430278
更新日期：2005-06-01 00:00:00
abstract：:Although a considerable number of papers have been published dealing with the frequency and variety of genetic and nongenetic limb defects in newborns and to a lesser extent among embryos, little has been published about the range of limb defects among spontaneously aborted middle and late-term fetuses. This study rep...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation that is characterized, in male patients, by psychomotor and growth retardation and various skeletal anomalies. Typical facial changes and specific clinical and radiological hand aspects exhibited by patients are essential clues for the diag...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/340607
更新日期：2002-06-01 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：:ATM, the gene that is mutated in ataxia-telangiectasia, is associated with cerebellar degeneration, abnormal proliferation of small blood vessels, and cancer. These clinically important manifestations have stimulated interest in defining the sequence variation in the ATM gene. Therefore, we undertook a comprehensive s...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/321296
更新日期：2001-08-01 00:00:00
abstract：:Premature ovarian failure (POF) is characterized by elevated gonadotropins and amenorrhea in women aged <40 years. In a Lebanese family with five sisters who received the diagnosis of POF, we established linkage to the long arm of the X chromosome (between Xq21.1 and Xq21.3.3), using whole-genome SNP typing and homozy...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/505406
更新日期：2006-07-01 00:00:00
abstract：:Cancer occurrence in 164 families with breast/ovarian cancer and germline BRCA2 mutations was studied to evaluate the evidence for genotype-phenotype correlations. Mutations in a central portion of the gene (the "ovarian cancer cluster region" [OCCR]) were associated with a significantly higher ratio of cases of ovari...
journal_title：American journal of human genetics
pub_type： 杂志文章,多中心研究
doi：10.1086/318181
更新日期：2001-02-01 00:00:00
abstract：:Obesity is an increasingly serious health problem in the world. Body mass index (BMI), percentage fat mass, and body fat mass are important indices of obesity. For a sample of pedigrees that contains >10,000 relative pairs (including 1,249 sib pairs) that are useful for linkage analyses, we performed a whole-genome li...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/339934
更新日期：2002-05-01 00:00:00
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 ...
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：:Analysis of human-Chinese hamster somatic cell hybrids with spontaneously derived chromosome structural changes has provided data for the regional and subregional localization of gene loci which have previously been assigned to human chromosomes 2, 12, and X. Correlation of the expression of human gene loci with the h...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1975-09-01 00:00:00
abstract：:Canavan disease is an autosomal recessive leukodystrophy caused by the deficiency of aspartoacylase (ASPA). Sixty-four probands were analyzed for mutations in the ASPA gene. Three point mutations--693C-->A, 854A-->C, and 914C-->A--were identified in the coding sequence. The 693C-->A and 914C-->A base changes, resultin...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:Esterase D (EsD), purified from human erythrocytes and tested with a variety of substrates, hydrolyzed only triacetin, tributyrin, and certain soluble aryl esters of aliphatic acids. Esters of 4-methylumbelliferone were easily the best substrates. When the three genetically different isozymes were compared, the less c...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:A patients with seizures, Von Willebrand disease, and symptoms of Turner syndrome was a chromosomal mosaic. In blood culture (1974), 56% of the cells were 45, X 33% 46, XXp+ and 11% 47,XXp + Xp +; in the skin, no cells with 47 chromosomes were found. Presumably the Xp + chromosome arose through a break in the Q-banded...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1977-01-01 00:00:00
abstract：:The practicality and moral value of community review of human genetic research has become a focus of debate. Examples from two Native American communities are used to address four aspects of that debate: (1) the value of community review in larger, geographically dispersed populations; (2) the identification of cultur...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302415
更新日期：1999-06-01 00:00:00
abstract：:A case of a 46,XYp- phenotypic female provided an opportunity to evaluate both sexual and somatic determinants for the Y chromosome. The patient had multiple stigmata of Turner syndrome, but normal stature. Laparotomy revealed a normal uterus and tubes, with 1.5 cm undifferentiated gonads. Serological tests for H-Y an...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1979-07-01 00:00:00
abstract：:Holoprosencephaly is the incomplete separation of the forebrain during embryogenesis. Both genetic and environmental etiologies have been determined for holoprosencephaly; however, a genetic etiology is not found in most cases. In this report, we present two unrelated individuals with semilobar holoprosencephaly who h...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.03.017
更新日期：2019-05-02 00:00:00
abstract：:In humans, recombination in the pseudoautosomal region is approximately 10-fold higher in males than in females. This difference is thought to reflect the fact that, in females, there is opportunity for genetic exchange along the entire length of the X chromosome, resulting in a relative reduction in the likelihood of...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-06-01 00:00:00
abstract：:Genetic risks are usually computed under the assumption that genetic parameters, such as the recombination fraction, are known without error. Uncertainty in the estimates of these parameters must translate into uncertainty regarding the risk. To allow for uncertainties in parameter values, one may employ Bayesian tech...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
