DNA mutation motifs in the genes associated with inherited
diseases

J 2017

DNA mutation motifs in the genes associated with inherited diseases

RŮŽIČKA, Michal, Petr KULHÁNEK, Lenka RADOVÁ, Andrea ČECHOVÁ, Naděžda ŠPAČKOVÁ et. al.

Základní údaje

Originální název

DNA mutation motifs in the genes associated with inherited diseases

Autoři

RŮŽIČKA, Michal (203 Česká republika, domácí), Petr KULHÁNEK (203 Česká republika, domácí), Lenka RADOVÁ (203 Česká republika, domácí), Andrea ČECHOVÁ (203 Česká republika, domácí), Naděžda ŠPAČKOVÁ (203 Česká republika, domácí), Lenka FAJKUSOVÁ (203 Česká republika, domácí) a Kamila RÉBLOVÁ (203 Česká republika, garant, domácí)

Vydání

Plos one, San Francisco, Public Library of Science, 2017, 1932-6203

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.766

Kód RIV

RIV/00216224:14740/17:00095121

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1371/journal.pone.0182377

UT WoS

000406768200074

Klíčová slova anglicky

REPAIR PROTEIN MUTS; MISMATCH REPAIR; STRAND ASYMMETRIES; CONFORMATIONAL-CHANGES; BENDING PROPENSITY; METHYLATION; RECOGNITION; MECHANISMS; HOTSPOTS; COMPLEX

Štítky

OA, rivok

Změněno: 1. 3. 2018 14:02, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role. To detect coldspots/hotspots unaffected by population bias, we analysed the presence of germline mutations obtained from HGMD database in the 5-nucleotide segments repeatedly occurring in genes associated with common inherited disorders, in particular, the PAH, LDLR, CFTR, F8, and F9 genes. Statistically significant sequences (mutational motifs) rarely associated with mutations (coldspots) and frequently associated with mutations (hotspots) exhibited characteristic sequence patterns, e.g. coldspots contained purine tract while hotspots showed alternating purine-pyrimidine bases, often with the presence of CpG dinucleotide. Using molecular dynamics simulations and free energy calculations, we analysed the global bending properties of two selected coldspots and two hotspots with a G/T mismatch. We observed that the coldspots were inherently more flexible than the hotspots. We assume that this property might be critical for effective mismatch repair as DNA with a mutation recognized by MutS alpha protein is noticeably bent.

Návaznosti

GA16-11619S, projekt VaV

Název: Základní vlastnosti DNA mutačních coldspotů/hotspotů v genech asociovaných s dědičnými chorobami

Investor: Grantová agentura ČR, Základní vlastnosti DNA mutačních coldspotů/hotspotů v genech asociovaných s dědičnými chorobami

LM2015085, projekt VaV

Název: CERIT Scientific Cloud (Akronym: CERIT-SC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CERIT Scientific Cloud

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

RŮŽIČKA, Michal, Petr KULHÁNEK, Lenka RADOVÁ, Andrea ČECHOVÁ, Naděžda ŠPAČKOVÁ, Lenka FAJKUSOVÁ a Kamila RÉBLOVÁ. DNA mutation motifs in the genes associated with inherited diseases. Plos one. San Francisco: Public Library of Science, 2017, roč. 12, č. 8, s. nestránkováno, 16 s. ISSN 1932-6203. Dostupné z: https://dx.doi.org/10.1371/journal.pone.0182377.

@article{1394050,
   author = {Růžička, Michal and Kulhánek, Petr and Radová, Lenka and Čechová, Andrea and Špačková, Naděžda and Fajkusová, Lenka and Réblová, Kamila},
   article_location = {San Francisco},
   article_number = {8},
   doi = {http://dx.doi.org/10.1371/journal.pone.0182377},
   keywords = {REPAIR PROTEIN MUTS; MISMATCH REPAIR; STRAND ASYMMETRIES; CONFORMATIONAL-CHANGES; BENDING PROPENSITY; METHYLATION; RECOGNITION; MECHANISMS; HOTSPOTS; COMPLEX},
   language = {eng},
   issn = {1932-6203},
   journal = {Plos one},
   title = {DNA mutation motifs in the genes associated with inherited diseases},
   url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377},
   volume = {12},
   year = {2017}
}

TY  - JOUR
ID  - 1394050
AU  - Růžička, Michal - Kulhánek, Petr - Radová, Lenka - Čechová, Andrea - Špačková, Naděžda - Fajkusová, Lenka - Réblová, Kamila
PY  - 2017
TI  - DNA mutation motifs in the genes associated with inherited diseases
JF  - Plos one
VL  - 12
IS  - 8
SP  - nestránkováno
EP  - nestránkováno
PB  - Public Library of Science
SN  - 19326203
KW  - REPAIR PROTEIN MUTS
KW  - MISMATCH REPAIR
KW  - STRAND ASYMMETRIES
KW  - CONFORMATIONAL-CHANGES
KW  - BENDING PROPENSITY
KW  - METHYLATION
KW  - RECOGNITION
KW  - MECHANISMS
KW  - HOTSPOTS
KW  - COMPLEX
UR  - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377
L2  - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377
N2  - Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role. To detect coldspots/hotspots unaffected by population bias, we analysed the presence of germline mutations obtained from HGMD database in the 5-nucleotide segments repeatedly occurring in genes associated with common inherited disorders, in particular, the PAH, LDLR, CFTR, F8, and F9 genes. Statistically significant sequences (mutational motifs) rarely associated with mutations (coldspots) and frequently associated with mutations (hotspots) exhibited characteristic sequence patterns, e.g. coldspots contained purine tract while hotspots showed alternating purine-pyrimidine bases, often with the presence of CpG dinucleotide. Using molecular dynamics simulations and free energy calculations, we analysed the global bending properties of two selected coldspots and two hotspots with a G/T mismatch. We observed that the coldspots were inherently more flexible than the hotspots. We assume that this property might be critical for effective mismatch repair as DNA with a mutation recognized by MutS alpha protein is noticeably bent.
ER  -

RŮŽIČKA, Michal, Petr KULHÁNEK, Lenka RADOVÁ, Andrea ČECHOVÁ, Naděžda ŠPAČKOVÁ, Lenka FAJKUSOVÁ a Kamila RÉBLOVÁ. DNA mutation motifs in the genes associated with inherited diseases. \textit{Plos one}. San Francisco: Public Library of Science, 2017, roč.~12, č.~8, s.~nestránkováno, 16 s. ISSN~1932-6203. Dostupné z: https://dx.doi.org/10.1371/journal.pone.0182377.

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