genetic variations
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1st ed. x, 265 s.
Genome-wide and candidate gene studies for pulmonary sarcoidosis have highlighted several candidate variants among different populations. However, the genetic basis of functional rare variants in sarcoidosis still needs to be explored. To identify functional rare variants in sarcoidosis, we sequenced exomes of 22 sarcoidosis cases from six families. Variants were prioritized using linkage and high-penetrance approaches, and filtered to identify novel and rare variants. Functional networking and pathway analysis of identified variants was performed using gene ontology based gene-phenotype, gene-gene, and protein-protein interactions. The linkage (n = 1007-7640) and high-penetrance (n = 11,432) prioritized variants were filtered to select variants with (a) reported allele frequency < 5% in databases (1.2-3.4%) or (b) novel (0.7-2.3%). Further selection based on functional properties and validation revealed a panel of 40 functional rare variants (33 from linkage region, 6 highly penetrant and 1 shared by both approaches). Functional network analysis implicated these gene variants in immune responses, such as regulation of pro-inflammatory cytokines including production of IFN-γ and anti-inflammatory cytokine IL-10, leukocyte proliferation, bacterial defence, and vesicle-mediated transport. The KEGG pathway analysis indicated inflammatory bowel disease as most relevant. This study highlights the subsets of functional rare gene variants involved in pulmonary sarcoidosis, such as, regulations of calcium ions, G-protein-coupled receptor, and immune system including retinoic acid binding. The implicated mechanisms in etiopathogenesis of familial sarcoidosis thus include Wnt signalling, inflammation mediated by chemokine and cytokine signalling and cadherin signalling pathways.
- MeSH
- celogenomová asociační studie MeSH
- exom * MeSH
- fenotyp MeSH
- genetická predispozice k nemoci * MeSH
- genetická variace * MeSH
- genetické markery * MeSH
- genotyp MeSH
- genové regulační sítě * MeSH
- lidé MeSH
- plicní sarkoidóza genetika patologie MeSH
- rodokmen MeSH
- sekvenční analýza DNA metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cambridge studies in biological anthropology ; 11
[1st ed.], repr xxiv, 354 s. . il.
454 s. : il.
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- embryologie a teratologie
- genetika, lékařská genetika
AIM: Estimating polymorphic allele frequencies of the NADPH-CYP450 oxidoreductase (POR) gene in a Czech Slavic population. METHODS: The POR gene was analyzed in 322 individuals from a control cohort by sequencing and high resolution melting analysis. RESULTS: We identified seven unreported SNP genetic variations, including two SNPs in the 5' flanking region (g.4965C>T and g.4994G>T), one intronic variant (c.1899-20C>T), one synonymous SNP (p.20Ala=) and three nonsynonymous SNPs (p.Thr29Ser, p.Pro384Leu and p.Thr529Met). The p.Pro384Leu variant exhibited reduced enzymatic activities compared with wild-type. CONCLUSION: New POR variant identification indicates the number of uncommon variants might be specific for each subpopulation being investigated, particularly germane to the singular role that POR plays in providing reducing equivalents to all CYP450s in the endoplasmic reticulum. Original submitted 15 September 2014; Revision submitted 17 November 2014.
- MeSH
- DNA genetika MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická variace MeSH
- haplotypy MeSH
- jednonukleotidový polymorfismus * MeSH
- kinetika MeSH
- kohortové studie MeSH
- konformace proteinů MeSH
- lidé MeSH
- missense mutace MeSH
- molekulární modely MeSH
- novorozenec MeSH
- sekvence nukleotidů MeSH
- substituce aminokyselin MeSH
- systém (enzymů) cytochromů P-450 chemie genetika metabolismus MeSH
- vazebná nerovnováha MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVES: The term "copy number variation/variant" (CNV) denotes a DNA sequence with a magnitude of 1 kb at least which is differently represented among individuals based on its deletion or duplication. Since 2008, multiple studies have reported copy number variations in schizophrenia, and they seem to fill in a gap in our knowledge on the genetic background of schizophrenia. The aim of this review is to sum up the current findings related to CNVs in schizophrenia in order to facilitate further research. METHODS: We searched the PubMed computer database using the key words "schizophrenia AND CNVs" on 26th October 2011. Out of 91 obtained results, we selected the references based on their relevance. RESULTS: The CNVs at genome loci 1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, 16p13.1 and 22q11.2 were associated with schizophrenia most frequently. The data provide evidence for low prevalent, but highly penetrant CNVs associated with schizophrenia. CNV deletions show higher penetrance than duplications. Larger CNVs often have higher penetrance than smaller CNVs. Although the vast majority of CNVs are inherited, CNVs that have newly occurred as de novo mutations have more readily been implicated in schizophrenia. De novo CNVs may be responsible for the presence of schizophrenia in only one of the two monozygotic twins, who otherwise have identical genomes. CONCLUSION: Identifying CNVs in schizophrenia can lead to changes in the treatment and genetic counselling. Our knowledge on the genetic background of neurodevelopmental disorders may also reduce stigma in schizophrenia.
- MeSH
- celogenomová asociační studie statistika a číselné údaje MeSH
- genetická predispozice k nemoci genetika MeSH
- genom lidský genetika MeSH
- lidé MeSH
- schizofrenie genetika MeSH
- variabilita počtu kopií segmentů DNA genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
v, 54 s. : il. ; 28 cm
- MeSH
- genetická variace MeSH
- genomika MeSH
- lékařská genetika MeSH
- výpočetní biologie MeSH
- Publikační typ
- sborníky MeSH
- Konspekt
- Obecná genetika. Obecná cytogenetika. Evoluce
- NLK Obory
- genetika, lékařská genetika
