Disease relevance of Genetic Heterogeneity

• With the first variant being defined, genetic heterogeneity has become apparent, as in other families parkinsonism was not linked to the 4q-locus and was not associated with the alpha-synuclein mutation (unpublished data) [1].
• We have demonstrated previously genetic heterogeneity within these disorders by excluding the disease locus from the documented spinocerebellar ataxia locus (SCA1) on chromosome 6p in a large Cuban founder population [2].
• The Silver syndrome variant of hereditary spastic paraplegia maps to chromosome 11q12-q14, with evidence for genetic heterogeneity within this subtype [3].
• To date, published linkage studies have provided no evidence of genetic heterogeneity in severe neonatal myotubular myopathy (XLMTM) [4].
• In conclusion, we hereby demonstrate further genetic heterogeneity of this Mendelian form of hypertension and identify a new PHA2C locus, the most compelling and precise linkage interval described to date [5].

Psychiatry related information on Genetic Heterogeneity

• These results point towards an etiological influence of TNFA alleles in narcolepsy and support previous findings suggesting genetic heterogeneity and differences in pathophysiological characteristics of HLA-DR2 positive and negative narcolepsy [6].

High impact information on Genetic Heterogeneity

• Although RYR1 mutations have been reported in many MHS human families, there is also significant genetic heterogeneity, and much less is known as to the underlying mechanism responsible for altered human myoplasmic Ca2+ regulation [7].
• Two individuals with Fraser syndrome were homozygous with respect to the same missense mutation of FREM2, confirming genetic heterogeneity [8].
• However, mutations in MADH4 are only present in a subset of JP cases, and although mutations in the gene for phosphatase and tensin homolog (PTEN) have been described in a few families, undefined genetic heterogeneity remains [9].
• We previously identified mutations of MSX2 in non-syndromic PFM and demonstrated genetic heterogeneity [10].
• Genetic heterogeneity of BFNC has been observed [11].

Chemical compound and disease context of Genetic Heterogeneity

• It is concluded that an excessive rise in circulating immunoreactive insulin in response to glucose is a common abnormality in dystrophia myotonica and reflects genetic heterogeneity in this condition [12].
• BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism with an extensive clinical and genetic heterogeneity [13].
• The possibility of genetic heterogeneity in maple syrup urine disease was investigated by measuring branched-chain ketoacid dehydrogenase in polyethylene glycol-induced heterokaryons of lymphoid cells [14].
• To investigate the effect of ribavirin on hepatitis C virus (HCV) infection, we analysed the evolution of the genetic heterogeneity of HCV in relation to the anti-HCV humoral response in patients treated by ribavirin alone [15].
• Parkinson's disease in Ireland: clinical presentation and genetic heterogeneity in patients with parkin mutations [16].

Biological context of Genetic Heterogeneity

• These results demonstrate linkage of the purely renal form of NPH to chromosome 2p, and suggest that there may be genetic heterogeneity between NPH and SLS [17].
• We have performed linkage analysis in 16 ARPKD families and localized the ARPKD gene to chromosomal region 6p21-cen with no evidence for genetic heterogeneity among different clinical phenotypes [18].
• These results suggest that mutations in at least four different genes lead to FA, a degree of genetic heterogeneity comparable to that of other DNA repair disorders [19].
• PDEA is the seventh RP gene identified, highlighting the extensive genetic heterogeneity of the disorder and encouraging further investigation into the role of other members of the phototransduction cascade in RP [20].
• Thus, with the combination of a subclinical marker (ANCAs) and molecular genetic markers, genetic heterogeneity has been demonstrated within UC: ANCA-positive UC associated with DR2, and ANCA-negative UC likely associated with DR4 [21].

Anatomical context of Genetic Heterogeneity

• We have previously demonstrated genetic heterogeneity in PS and mapped a gene to chromosome 8 (ref. 3) and a second to chromosome 10 (ref. 4). The gene on chromosome 8 is the fibroblast growth factor receptor 1 (FGFR1) with a common mutation (C755G) predicting a Pro252Arg substitution [22].
• In both cases the Alien Antigens are also artefacts, resulting from genetic heterogeneity in either mice or cell lines [23].
• Germ-line mosaicism simulates genetic heterogeneity in Wiskott-Aldrich syndrome [24].
• CFTR haplotype analysis reveals genetic heterogeneity in the etiology of congenital bilateral aplasia of the vas deferens [25].
• Elsewhere, we have identified PLOSL mutations in TYROBP (DAP12), which codes for a membrane receptor component in natural-killer and myeloid cells, and also have identified genetic heterogeneity in PLOSL, with some patients carrying no mutations in TYROBP [26].

Associations of Genetic Heterogeneity with chemical compounds

• Genetic heterogeneity, technical differences of differences in plasma homocystine concentrations could account for these descrepant results [27].
• Human cytochrome P450 isoforms. Their genetic heterogeneity and induction by omeprazole [28].
• Androgen insensitivity in man: evidence for genetic heterogeneity [29].
• In conclusion, we report the unique clinical findings and linkage-analysis results of 16 patients with Wolfram syndrome and provide further evidence for the genetic heterogeneity of this disorder [30].
• Genetic heterogeneity of GA has been suggested by the demonstration that administration of pyridoxine to increase the level of pyridoxal phosphate, a cofactor of OATase, reduces hyperornithinemia in a subset of patients [31].

Gene context of Genetic Heterogeneity

• This work emphasizes the genetic heterogeneity of juvenile glaucoma and suggests, for the first time, that (1) congenital glaucoma and juvenile glaucoma are allelic variants and (2) the spectrum of expression of MYOC and CYP1B1 mutations is greater than expected [32].
• Our results show that mutations in the gene for Cx30.3 can be causally involved in EKV and point to genetic heterogeneity of this disorder [33].
• Genetic heterogeneity has been confirmed as an explanation for such failure, since causative mutations have been identified in the COL5A1, COL5A2, and tenascin X genes and since they have been inferred in the COL1A2 gene [34].
• The identification of germline mutations in families with HNPCC is hampered by genetic heterogeneity and clinical variability [35].
• The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers [36].

Analytical, diagnostic and therapeutic context of Genetic Heterogeneity

• These linkage data and the absence of genetic heterogeneity in all families tested to date have important implications for DNA-based prenatal diagnoses as well as for the isolation of the ARPKD gene [37].
• As part of an analysis of pretreatment variables that might affect the outcome of treatment, genetic heterogeneity within the viral E1-E2 glycoprotein region (nucleotides 851 to 2280) was assessed by sequencing 10 to 15 quasispecies clones per patient from serum-derived PCR products [38].
• Formalin-fixed and paraffin-embedded tissue sections of 10 GBM were evaluated for intratumoral genetic heterogeneity by microdissection of multiple areas of 20-50 tumor cells and DOP-PCR of DNA isolated from the dissected cell groups, followed by comparative genomic hybridization (CGH) [39].
• To address the issue of genetic heterogeneity, and to study the pathogenesis of these DOC, skin biopsies from eight CIE, three LI, and six normal subjects were assessed by electron microscopy, including ruthenium tetroxide postfixation with optical diffraction, to visualize and quantitate intercellular membrane domains [40].
• The genetic heterogeneity was also denoted by pulsed-field gel electrophoresis analysis that showed 24 different pulsotypes among the 57 MRSA isolates [41].

References