Search results for "zygosity"
showing 10 items of 200 documents
Genetics of retinoblastoma: A study
1997
Abstract We have analyzed 43 families with either familial retinoblastoma (RB) (four kindreds), bilateral sporadic RB (10 individuals), or unilateral sporadic RB (29 individuals). Genetic studies focused on karyotype analysis, loss of heterozygosity of intragenic polymorphisms, and search for point mutations. We have been able to identify the genetic defect underlying the disease in eight cases. Deletions have been found in three patients with sporadic RB, two bilateral in one of which karyotyping had previously detected an interstitial deletion of chromosome 13 affecting (q13–q31) and one unilateral. Five different point mutations were responsible for three cases of bilateral sporadic RB, …
Deficient membrane integration of the novel p.N14D-GJB2mutant associated with non-syndromic hearing impairment
2006
Mutations in GJB2, the gene encoding for the Gap Junction protein Connexin 26 (Cx26), have been established as the major cause of hereditary, non-syndromic hearing impairment (HI). We report here the identification of a novel point mutation in GJB2, c.40A>G [p.N14D], detected in compound heterozygosity with the c.35delG mutation in two brothers with moderate non-syndromic sensorineural HI. The mother who carried one wildtype and a p.N14D allele displayed normal hearing. The mutation leads to substitution of the neutral amino acid asparagine (N) by the negatively charged aspartic acid (D) at amino acid number 14, a position that is conserved among Cx26 of different organisms and among many o…
Mutations inWNT10Aare frequently involved in oligodontia associated with minor signs of ectodermal dysplasia
2012
Ectodermal dysplasias (ED) are a clinically and genetically heterogeneous group of hereditary disorders that have in common abnormal development of ectodermal derivatives. Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of eccrine sweat glands, hair, and teeth. The X-linked form of the disease, caused by mutations in the EDA gene, represents the majority of patients with the hypohidrotic form. Autosomal dominant and autosomal recessive forms are occasionally seen, and result from mutations in at least three genes (WNT10A, EDAR, or more rarely EDARADD). We have screened for mutations in EDAR (commonly involved in the hypohidrotic form) and WNT10A (involved in…
Exploring by whole exome sequencing patients with initial diagnosis of Rubinstein-Taybi syndrome: the interconnections of epigenetic machinery disord…
2019
Rubinstein–Taybi syndrome (RSTS) is an autosomal-dominant neurodevelopmental disease affecting 1:125,000 newborns characterized by intellectual disability, growth retardation, facial dysmorphisms and skeletal abnormalities. RSTS is caused by mutations in genes encoding for writers of the epigenetic machinery: CREBBP (~ 60%) or its homologous EP300 (~ 10%). No causative mutation is identified in up to 30% of patients. We performed whole-exome sequencing (WES) on eight RSTS-like individuals who had normal high-resolution array CGH testing and were CREBBP- and EP300-mutation -negative, to identify the molecular cause. In four cases, we identified putatively causal variants in three genes (ASXL…
Signatures of selection in the genome of Swedish warmblood horses selected for sport performance
2019
Abstract Background A growing demand for improved physical skills and mental attitude in modern sport horses has led to strong selection for performance in many warmblood studbooks. The aim of this study was to detect genomic regions with low diversity, and therefore potentially under selection, in Swedish Warmblood horses (SWB) by analysing high-density SNP data. To investigate if such signatures could be the result of selection for equestrian sport performance, we compared our SWB SNP data with those from Exmoor ponies, a horse breed not selected for sport performance traits. Results The genomic scan for homozygous regions identified long runs of homozygosity (ROH) shared by more than 85%…
Evidence for an Association between Post-Fledging Dispersal and Microsatellite Multilocus Heterozygosity in a Large Population of Greater Flamingos
2013
10 pages; International audience; DISPERSAL CAN BE DIVIDED INTO THREE STAGES: departure, transience and settlement. Despite the fact that theoretical studies have emphasized the importance of heterozygosity on dispersal strategies, empirical evidence of its effect on different stages of dispersal is lacking. Here, using multi-event capture-mark-recapture models, we show a negative association between microsatellite multilocus heterozygosity (MLH; 10 loci; n = 1023) and post-fledging dispersal propensity for greater flamingos, Phoenicopterus roseus, born in southern France. We propose that the negative effects of inbreeding depression affects competitive ability and therefore more homozygous…
Cathepsin C gene: First compound heterozygous patient with Papillon-Lefèvre syndrome and a novel symptomless mutation.
2001
Papillon-Lefevre syndrome (PLS) has recently been shown to be caused by mutations in the cathepsin C gene resulting in periodontal disease and palmoplantar keratosis. Thirteen different homozygous mutations have been characterised in PLS patients of different ethnic origin. In the present paper, a PLS patient is described who carries two novel mutations (706G>T and 872G>A) in the paternal and maternal chromosomes, respectively. This is the first compound patient described so far. In addition, a novel symptomless mutation (458C>T) in the cathepsin C gene is described in three homozygous individuals. Thus, not all mutations should be considered as a cause of disease, whether case studies or g…
Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutation.
2003
Item does not contain fulltext A boy with recurrent episodes of hypoglycaemia and ataxia, microcephaly, mental retardation, permanent lactic acidaemia, intermittent 2-oxoglutaric aciduria as well as elevation of serum branched chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3) deficiency. Analysis of genomic DNA revealed compound heterozygosity for two novel mutations: I393T in exon 11, located at the interface domain of the protein and possibly interfering with its dimerisation, and IVS9+1G>A located at a consensus splice site. A heterozygous polymorphism was also detected. In the patient's cDNA the I393T mutation and the polymorphism appeared to be homozygous, indica…
Inbreeding depression and male fitness in black grouse
2002
The male lifetime lekking performance was studied, and related to inbreeding-outbreeding in a wild population of black grouse (Tetrao tetrix) in central Finland between 1989 and 1995. Inbreeding was measured as the mean heterozygosity and mean d(2) of 15 microsatellite loci. We found a significantly positive relationship between mean d(2) and lifetime copulation success (LCS), while the relationship between heterozygosity and LCS was close to significant. We also found that males that never obtained a lek territory had significantly lower mean heterozygosity than males that were observed on a territory at least during one mating season in their life. Furthermore, among males that were succe…
Compound heterozygosity in the SPG4 gene causes hereditary spastic paraplegia
2008
The SPG4 gene is frequently mutated in autosomal dominant form of hereditary spastic paraplegia (HSP). We report that the compound heterozygous sequence variants S44L, a known polymorphism, and c.1687G>A, a novel mutation in SPG4 cause a severe form of HSP in a patient. The family members carrying solely c.1687G>A mutation are asymptomatic for HSP. The reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the c.1687G>A mutation is a splice site mutation and causes skipping of the exon 15 of spastin. Furthermore, quantification of RT-PCR products by sequencing and quantification of allele-specific expression by pyrosequencing assay revealed that c.1687G>A is a leaky…