Whole Exome Sequencing Study in Isolated South-Eastern Moravia (Czechia) Population Indicates Heterogenous Genetic Background for Parkinsonism Development

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F22%3A10157191" target="_blank" >RIV/00098892:_____/22:10157191 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/22:73615480

Výsledek na webu

<a href="http://www.frontiersin.org/articles/10.3389/fnins.2022.817713/full" target="_blank" >http://www.frontiersin.org/articles/10.3389/fnins.2022.817713/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fnins.2022.817713" target="_blank" >10.3389/fnins.2022.817713</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Whole Exome Sequencing Study in Isolated South-Eastern Moravia (Czechia) Population Indicates Heterogenous Genetic Background for Parkinsonism Development

Popis výsledku v původním jazyce

Parkinsonism belongs to the most common neurodegenerative disease. Genetic predisposition could be one of the significant risk factor for disease development. It has been described higher prevalence of parkinsonism in large pedigree from southeastern Moravia region. The study aims were to select accessible subfamily trios from the pedigree suitable for segregation genetic analyses to perform whole exome sequencing (WES) in trio individuals and further to evaluate genetic variants in the each trio. We used IonTorrent platform for WES for five subfamily trios (1-5). Each trio included two affected and one healthy person (as control). Found variants were filtered with respect to MAF &lt; 1% (minor allele frequency), variants effect (based on prediction tools) and disease filter (Parkinsonism responsible genes). Finally, the variants from each trio were assessed with respect to the presence in the patients. There were found no one founder mutation in the subfamilies from the pedigree. Trio 1 shares two variants with trio 2:MC1R:c.322G &gt; A (p.A108T) and MTCL1:c.1445C &gt; T (p.A482V), trio 3 shares two variants with trio 5: DNAJC6:c.1817A &gt; C (p.H606P) and HIVEP3:c.3856C &gt; A (p.R1286W). In trios 4 and 5, there were found two variants in gene CSMD1:c.3335A &gt; G (p.E1112G) and c.4071C &gt; G (p.I1357M) respectively. As the most potentially damaging, we evaluated the non-shared variant SLC18A2:c.583G &gt; A (p.G195S). The variant could affect dopamine transport in dopaminergic neurons. The study of the parkinsonism genetic background in isolated Moravian population suggested that there could be significant accumulation of many risk genetic factors. For verification of the variants influence, it would be appropriate to perform a more extensive population study and suitable functional analysis

Název v anglickém jazyce

Whole Exome Sequencing Study in Isolated South-Eastern Moravia (Czechia) Population Indicates Heterogenous Genetic Background for Parkinsonism Development

Popis výsledku anglicky

Parkinsonism belongs to the most common neurodegenerative disease. Genetic predisposition could be one of the significant risk factor for disease development. It has been described higher prevalence of parkinsonism in large pedigree from southeastern Moravia region. The study aims were to select accessible subfamily trios from the pedigree suitable for segregation genetic analyses to perform whole exome sequencing (WES) in trio individuals and further to evaluate genetic variants in the each trio. We used IonTorrent platform for WES for five subfamily trios (1-5). Each trio included two affected and one healthy person (as control). Found variants were filtered with respect to MAF &lt; 1% (minor allele frequency), variants effect (based on prediction tools) and disease filter (Parkinsonism responsible genes). Finally, the variants from each trio were assessed with respect to the presence in the patients. There were found no one founder mutation in the subfamilies from the pedigree. Trio 1 shares two variants with trio 2:MC1R:c.322G &gt; A (p.A108T) and MTCL1:c.1445C &gt; T (p.A482V), trio 3 shares two variants with trio 5: DNAJC6:c.1817A &gt; C (p.H606P) and HIVEP3:c.3856C &gt; A (p.R1286W). In trios 4 and 5, there were found two variants in gene CSMD1:c.3335A &gt; G (p.E1112G) and c.4071C &gt; G (p.I1357M) respectively. As the most potentially damaging, we evaluated the non-shared variant SLC18A2:c.583G &gt; A (p.G195S). The variant could affect dopamine transport in dopaminergic neurons. The study of the parkinsonism genetic background in isolated Moravian population suggested that there could be significant accumulation of many risk genetic factors. For verification of the variants influence, it would be appropriate to perform a more extensive population study and suitable functional analysis

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Neuroscience

ISSN

1662-453X

e-ISSN

1662-453X

Svazek periodika

16

Číslo periodika v rámci svazku

March

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

7

Strana od-do

817713

Kód UT WoS článku

000778996200001

EID výsledku v databázi Scopus

2-s2.0-85127914693