ライフサイエンスコーパス: de novo mutation

1 henomenon relates to genome-wide patterns of de novo mutation.

2 CR) to validate heteroplasmies and confirm a de novo mutation.

3 Eight patients had de novo mutations.

4 le, we sequenced them in parents to identify de novo mutations.

5 5% of NSC is sporadic, suggesting a role for de novo mutations.

6 the recurrence risks of disorders caused by de novo mutations.

7 egy for discovery and analysis of pathogenic de novo mutations.

8 test to identify gene-specific enrichment of de novo mutations.

9 arkedly alters the frequency and spectrum of de novo mutations.

10 the variants were demonstrated to represent de novo mutations.

11 ts with typical PD to unequivocally identify de novo mutations.

12 h a positive family history can also harbour de novo mutations.

13 cases of ASD/ID are enriched for disruptive de novo mutations.

14 lue of gene-set analysis, and the utility of de novo mutations.

15 selection on standing genetic variation and de novo mutations.

16 ve a negative family history with apparently de novo mutations.

17 argest family (LOD = 8.3) to three confirmed de novo mutations.

18 of 20 STATseq diagnoses were associated with de-novo mutations.

19 ly a minority of the observed excess of such de novo mutations(1,2).

20 urgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five d

21 During aging, de novo mutations accumulate in the male germline and ar

22 ent common ancestor offer a way to ascertain de novo mutations across multiple generations.

23 or mechanisms that can lead from accumulated de novo mutations across tissues to cell functional loss

24 ected families, as well as another recurrent de novo mutation affecting the same amino acid in ten in

25 Notably, likely gene-disrupting (LGD) de novo mutations affecting the same gene often result i

26 Here, we report de novo mutations affecting two genes, PLXND1 and REV3L

27 In summary, recurrent de novo mutations, affecting the highly conserved residu

28 However, the lack of de novo mutation and high-resolution nucleosome data has

29 esulted from a genetic interaction between a de novo mutation and one or more cryptic variants.

30 PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk

31 addition of CHK1i to AraC does not generate de novo mutations and in patients' samples where AraC is

32 understand the impact of disease-associated de novo mutations and other rare sequence variants on TR

33 We confirmed 48 de novo mutations and, based on best biological evidence

34 was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63

35 ate of increase in heteroplasmy variance and de novo mutation are proportionally modulated by the (ph

36 derlying some case of sporadic ALS, and that de novo mutations are also likely to play a part in the

37 Overall, we find strong evidence that de novo mutations are associated with ASD apart from the

38 Germline de novo mutations are the basis of evolutionary diversit

39 Nevertheless, how de novo mutations arise remains poorly understood.

40 De novo mutations arising on the paternal chromosome mak

41 ears, particularly with the demonstration of de novo mutations as an important source of causality.

42 ng has implicated large numbers of genes and de novo mutations as potential disease risk factors.

43 We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not descr

44 We identify SLC12A2 de novo mutations as the cause of a novel neurodevelopme

45 sing experimentally validated true and false de novo mutations as well as collected false de novo mut

46 is significantly enriched for non-synonymous de novo mutations ascertained from patients with monogen

47 endelian disorders and the prioritization of de novo mutations associated with complex neurodevelopme

48 ive different genes exhibiting a significant de novo mutation burden.

49 d infantile spasms did not reveal additional de novo mutations, but detected a carrier of a novel inh

50 The probability of observing 13 or more de novo mutations by chance among 5,855 individuals is v

51 s in sex and IQ in affected individuals with de novo mutations by matching probands with and without

52 We identified 11 additional de novo mutations by sequencing DNMT3A in a further 142

53 nome sequencing, we identified the recurrent de novo mutations c.650G>A (p.Arg217His) and c.649C>T (p

54 in two dominant FEVR-affected families and a de novo mutation (c.1434_1435insC [p.Glu479Argfs( *)18])

55 3K7, including one highly recurrent (n = 15) de novo mutation (c.1454C>T [ p.Pro485Leu]) proximal to

56 Remarkably, a recurrent de novo mutation, c.959G>A (p.Arg320His), in KCNC1 was i

57 r improvement with regard to the accuracy of de novo mutation calling.

58 re we show that the same mutations as inborn de novo mutations cause an early onset multisystem disor

59 We applied this framework to de novo mutations collected from 1,078 ASD family trios,

60 gests that both truncating and nontruncating de novo mutations contribute to autism, with a bias agai

61 ural stem cell renewal, we hypothesized that de novo mutations controlling embryonic development, in

62 When analyzing large de novo mutation datasets in humans, we find multiple li

63 We have applied this approach to four de novo mutation datasets of neurodevelopmental and neur

64 NMFilter could be coupled with commonly used de novo mutation detection approaches as an effective fi

65 le cell is required for applications such as de novo mutation detection, linkage analysis and lineage

66 wide association studies, approximately 1000 de novo mutations discovered by large-scale sequencing o

67 n apply a different inheritance pattern or a de novo mutations discovery model to each family and sel

68 We combined de novo mutation (DNM) data from 10,927 individuals with

69 We performed de novo mutation (DNM) screening on 24 HSCR trios.

70 of >=10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental di

71 De novo mutations (DNMs) accounted for 8% of cases, incl

72 We focused our attention on de novo mutations (DNMs) and identified candidate genes

73 ly 2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance.

74 Human germline de novo mutations (DNMs) are both a driver of evolution

75 De novo mutations (DNMs) are increasingly recognized as

76 Although de novo mutations (DNMs) are known to increase an indivi

77 Protein-coding de novo mutations (DNMs) are significant risk factors in

78 ers (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-co

79 The number of de novo mutations (DNMs) found in an offspring's genome

80 By retrieving 1725 exonic de novo mutations (DNMs) from 1628 subjects with autisti

81 and congenital heart disease (CHD) which use de novo mutations (DNMs) from parent-offspring trios hav

82 While genes with an excess of de novo mutations (DNMs) have been identified in childre

83 hinese ASD probands and detected 22 damaging de novo mutations (DNMs) in 20 genes, including CHD8 and

84 Recent studies of de novo mutations (DNMs) in schizophrenia and autism hav

85 Identifying de novo mutations (DNMs) in sporadic cases provides an e

86 De novo mutations (DNMs) originating in gametogenesis ar

87 e sequencing data set of 36,441 high-quality de novo mutations (DNMs) that arose in 816 family trios

88 De novo mutations (DNMs), or mutations that appear in an

89 variants (CNVs), of which 133,992 and 88 are de novo mutations (DNMs), respectively.

90 genome sequencing (WGS) to identify numerous de novo mutations (DNMs).

91 maining cases, the phenotype arose without a de novo mutation due to two different classes of higher-

92 t (MDR) tuberculosis can be acquired through de-novo mutation during tuberculosis treatment or throug

93 common and low-frequency genetic variations, de novo mutations, epigenetic changes, somatic mutations

94 ios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed

95 it to characterize the rate and spectrum of de novo mutation events in 119 progeny from four Plasmod

96 Moreover, previous analyses of germline de novo mutations examined pedigrees (and not germ cells

97 n both saliva and blood and ~3% of causative de novo mutations exhibit PZM; this is an important obse

98 Previously identified putative de novo mutations failed to complement yeast strains lac

99 acquire beneficial alleles via selection or de novo mutation for future adaptation.

100 by a novel mathematical model incorporating de novo mutations for both species.

101 were preferentially disrupted by deleterious de novo mutations for monogenic epilepsy, in line with t

102 bility of our approach to identify causative de novo mutations for these complex diseases.

103 de novo mutations as well as collected false de novo mutations from an in-house large-scale exome-seq

104 We also show that de novo mutations from independent MA experiments displa

105 nerate a data set for this purpose using (1) de novo mutations from mutation accumulation experiments

106 Here we analyze 11,020 de novo mutations from the whole genomes of 250 families

107 Spontaneously arising (de novo) mutations have an important role in medical gen

108 The genetic synaptopathy caused by VAMP2 de novo mutations highlights the key roles of this gene

109 De novo mutations (i.e. newly occurring mutations) are a

110 lable from unaffected parents, we discovered de novo mutations, implicating genes, including CHD3, SE

111 We investigated de novo mutation in 1163 Staphylococcus aureus genomes f

112 The identification of a novel de novo mutation in a biologically-relevant candidate ge

113 well as the identification of a heterozygous de novo mutation in CDC42, i.e., p.Tyr64Cys.

114 We identified a de novo mutation in FRIZZLED2 (FZD2) in the proband and

115 A de novo mutation in GARS was identified in a patient wit

116 th severe encephalopathy carrying a missense de novo mutation in GRIN2B(p.P553T) coding for the GluN2

117 We identified a causal de novo mutation in keratin 1 (KRT1).

118 unknown genetic disorder caused by the same de novo mutation in LEMD2 (c.1436C>T;p.Ser479Phe), the g

119 We show that a recurrent de novo mutation in LEMD2 causes a nuclear envelopathy w

120 Direct observation of de novo mutation in multigeneration families suggests th

121 ents are often found to carry a heterozygous de novo mutation in one of the genes associated with the

122 e-Carpenter syndrome is caused by a specific de novo mutation in P4HB that impairs the disulfide isom

123 -Marie-Tooth disease type 1 and identified a de novo mutation in PMP2, the gene that encodes the myel

124 iduals with mild to profound ID and DD and a de novo mutation in PPP2CA, encoding the catalytic Calph

125 Additionally, a sixth individual with a de novo mutation in PPP3CA was connected to this study t

126 dysmorphic features (3/6), each harboring a de novo mutation in PPP3CA.

127 ted to genes already implicated in NDDs, but de novo mutation in such elements is estimated to accoun

128 Vs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30 C > G (p.Phe10Leu)], a

129 We discovered that one autism-associated de novo mutation in TGEF1 (K1431M), at the TGEF1/Rac1 in

130 at [KIL-d] selectively increases the rate of de novo mutation in the killer toxin gene of the viral g

131 s and SUDEP, confirming the causality of the de novo mutation in the proband.

132 An ASD-associated de novo mutation in the SLC6A3 gene resulting in a threo

133 disease revealed that they all had the same de novo mutation in TUBB4A, which encodes tubulin beta-4

134 We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affe

135 Recent meta-analyses statistically analyzing de novo mutations in >7,000 individuals with neurodevelo

136 ,133 schizophrenia cases and 9,274 controls, de novo mutations in 1,077 family trios, and copy number

137 ealed 15 probands with heterozygous damaging de novo mutations in 12 negative regulators of Wnt, BMP,

138 Overall, we find significant clustering of de novo mutations in 200 genes, highlighting specific fu

139 We have identified and confirmed 20 coding de novo mutations in 21 trios.

140 enome maintenance processes and characterize de novo mutations in 274 diploid Saccharomyces cerevisia

141 We searched for de novo mutations in a family quartet with a sporadic ca

142 ASD postmortem brains and in genes harboring de novo mutations in ASD.

143 th IQ above 100, suggesting that the role of de novo mutations in ASDs might reside in fundamental ne

144 we provide strong evidence that prioritized de novo mutations in autism probands point to a small se

145 ric probands who carry damaging heterozygous de novo mutations in CAPZA2 (HGNC: 1490) and exhibit neu

146 wo patients with NSEOE had likely pathogenic de novo mutations in CBL and CSNK1G1, respectively.

147 g trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases.

148 De novo mutations in CHD8 are strongly associated with a

149 ied by mutation accumulation leading to more de novo mutations in children born to older mothers.

150 trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play

151 this study we present 35 unique deleterious de novo mutations in DDX3X identified by whole exome seq

152 dentified 18 patients with likely diagnostic de novo mutations in dominant DD-associated genes at non

153 Here, we report that de novo mutations in EBF3 cause a complex neurodevelopme

154 Heterozygous de novo mutations in EEF1A2, encoding the tissue-specifi

155 Heterozygous de novo mutations in FOXJ1, which encodes a well-known m

156 phrenia patients were found to have enriched de novo mutations in genes belonging to the postsynaptic

157 Interestingly, de novo mutations in genes encoding A- and B-type subuni

158 detection of true positives (i.e., assessing de novo mutations in genes likely to be disease causing)

159 etic aetiology and are often associated with de novo mutations in genes mediating synaptic transmissi

160 pothesis that CTRD is caused by inherited or de novo mutations in genes required for normal tracheal

161 We revealed de novo mutations in GRIN2B encoding the NR2B subunit of

162 lites, are among the largest contributors of de novo mutations in humans.

163 Trio-based exome sequencing identified de novo mutations in ITPR1 in three unrelated individual

164 ion sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium chann

165 Here we report damaging de novo mutations in KCNH1 (encoding a protein called et

166 h significant spatial clustering patterns of de novo mutations in large cohorts.

167 m this hypothesis with the identification of de novo mutations in LMNB1 in seven individuals with pro

168 Our findings collectively indicate that de novo mutations in LMNB1 result in a dominant and dama

169 e duplex sequencing to detect low-frequency, de novo mutations in mitochondrial DNA (mtDNA) directly

170 We hypothesized that de novo mutations in mitochondrial DNA (mtDNA), which ha

171 s where genetic causes have been identified, de novo mutations in neuronally expressed genes are a co

172 ons and was overtransmitted to patients with de novo mutations in other genes in these pathways, supp

173 r a proportion of MBS patients suggests that de novo mutations in other genes might account for other

174 genome-wide mutation rate have been counting de novo mutations in parent-offspring trios and comparin

175 the utility of the approach for analysis of de novo mutations in parents/child families.

176 network containing proteins found to harbor de novo mutations in patients affected by schizophrenia

177 rained genes in healthy subjects, and excess de novo mutations in patients highlighted particular pos

178 enriched for genes that harbor nonsynonymous de novo mutations in patients with epileptic encephalopa

179 ifying disease-associated genes by detecting de novo mutations in patients.

180 e has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite popu

181 velopment to discover "modules" enriched for de novo mutations in probands.

182 De novo mutations in protein-coding genes are a well-est

183 velopmental disorders, much of the excess of de novo mutations in protein-coding genes remains unacco

184 eatures of 5q31.3 microdeletion syndrome and de novo mutations in PURA, encoding transcriptional acti

185 The characterization of de novo mutations in regions of high sequence and struct

186 in the global influenza population begin as de novo mutations in single infected hosts, but the evol

187 Through trio exome sequencing we identified de novo mutations in SLC12A2 in six children with neurod

188 De novo mutations in specific mTOR pathway genes cause b

189 WGS can be used to accurately identify these de novo mutations in spite of the thousands of false-pos

190 These findings support the hypothesis that de novo mutations in sporadic autism have severe functio

191 ree genes in PD and suggest that testing for de novo mutations in sporadic disease may aid in the ide

192 riant prioritization methods when evaluating de novo mutations in studies of autosomal dominant disea

193 hogenic mutations were identified, including de novo mutations in STXBP1, CASK and ALG13, as well as

194 ia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neuro

195 transmitted account for 6.8% of the presumed de novo mutations in the children.

196 sively parallel sequencing has revealed many de novo mutations in the etiology of developmental and e

197 he Epi4K consortium recently identified four de novo mutations in the gamma-aminobutyric acid type A

198 Here the authors identify a large cluster of de novo mutations in the GEF1 domain of Trio in whole-ex

199 geted search, we identified an enrichment of de novo mutations in the gene encoding the 330-kDa tripl

200 Recently, de novo mutations in the gene KCNA2, causing either a do

201 De novo mutations in the guanine nucleotide-binding prot

202 ting neurological disorder that results from de novo mutations in the Na channel Nav1.6.

203 We show that de novo mutations in the offspring of older fathers are

204 Simons Simplex Collection carrying damaging de novo mutations in these genes exhibit increased aberr

205 Patients with de novo mutations in these modules are more significantl

206 ar genetic basis of PME and show the role of de novo mutations in this disease entity.

207 Here we present 19 de novo mutations in this gene, including five missense

208 Ten de novo mutations in three previously identified disease

209 , we discover a large cluster of ASD-related de novo mutations in Trio's Rac1 activating domain, GEF1

210 crimination/associative learning, unlike the de novo mutations in unaffected siblings.

211 Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals pres

212 recent studies have investigated the role of de novo mutations in various neurodevelopmental and neur

213 ocalization score for brain tissues to score de novo mutations in whole genomes from 1,902 individual

214 missense mutations in this gene, including a de-novo mutation in the receptor pore region (GluN2A(N61

215 However, new (de novo) mutations, in the form of large chromosomal cop

216 PPP2CA de novo mutations included a partial gene deletion, a fr

217 Some blood isolates also contained de novo mutations, including a non-synonymous SNP confer

218 ion patterns in families due to causation by de novo mutations, incomplete penetrance, and/or variabl

219 sm spectrum disorders recurrence risk due to de novo mutations into a vast majority with near 0% recu

220 m spectrum disorders (ASDs), the signal from de novo mutations is distributed across many genes, maki

221 The number of de novo mutations is extremely low with maximum pairwise

222 Current knowledge about de novo mutations is incomplete and mostly indirect.

223 dominant monogenic disorders associated with de novo mutations is not available, despite their relati

224 ich allows genome-wide detection of rare and de novo mutations, is transforming neuropsychiatric dise

225 Postzygotic de novo mutations lead to the phenomenon of gene mosaici

226 sweeps within the last few thousand years on de novo mutations, mainly in noncoding regions.

227 Here, we hypothesized that de novo mutations may account for a proportion of these

228 d connectivity and that its dysregulation by de novo mutations may be a potential determinant of 16p1

229 Children with ASD with de novo mutations may exhibit a "muted" symptom profile

230 Recent studies suggest de novo mutations may involve the pathogenesis of autism

231 Among 41 patients with de novo mutations, MEN 2B was diagnosed in 12 patients a

232 her-mother-offspring constellations to study de novo mutations, minisatellite mutations, copy-number

233 nosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mos

234 Children with de novo mutations (N=112) had a greater likelihood of mo

235 We show that noncoding de novo mutations near genes co-expressed in midfetal br

236 sm indicating that a large fraction of these de novo mutations occurred during early germ cell develo

237 esis are often considered the consequence of de novo mutations occurring in the tumour.

238 s describing the genetic association between de novo mutations of NMDAR subunits and severe psychiatr

239 d post-transcriptional-regulation-disrupting de novo mutations of significantly higher functional imp

240 It is primarily caused by de novo mutations of the SCN1A gene encoding a neuronal

241 De novo mutations of the sodium channel gene SCN8A resul

242 De novo mutations of the sodium channel gene SCN8A, enco

243 De novo mutations of the voltage-gated sodium channel ge

244 Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met

245 istent loss-of-function effect of all tested de novo mutations on the Wnt pathway, and we further sho

246 ales with ID, but there is less evidence for de novo mutations on the X chromosome causing ID in fema

247 uency loss of the functional EFG1 allele via de novo mutation or gene conversion events.

248 We have identified 23 individuals with de novo mutations or deletions of YY1 and phenotypic fea

249 ncluding 38 new NDD genes, with an excess of de novo mutations or private disruptive mutations in 5.7

250 may be a consequence of sexual transmission, de novo mutations, or technical errors in identification

251 nse mutations when compared to probands with de novo mutations outside of these modules.

252 The de novo mutation p.Val404Met is novel and occurs at a hi

253 ion of 12,916 genes under a model of neutral de novo mutation (p<10-4).

254 ing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene.

255 ating mutations (P=0.00851) and an excess of de novo mutations (P=2.53 x 10(-10)) among ASD/intellect

256 A whole-exome sequencing study identified a de novo mutation, p.A749G, in Cav1.3 alpha1-subunits (CA

257 Our results also suggest that truncating de novo mutations play a smaller role in the etiology of

258 Spontaneous (de novo) mutations play an important role in the disease

259 developmental diseases for which rare, often de novo, mutations play a significant role in disease ri

260 For genes that harbor de novo mutations predicted to be deleterious, we found

261 variant(s) for individuals with inherited or de novo mutations presents one of the main challenges fa

262 We identified de novo mutations, previously reported pathogenic mutati

263 Of the genes identified to carry de novo mutations, PTEN, VAPB and ASNA1 are supported by

264 Origin of these variants, including de novo mutation rate and extent of founder versus recur

265 Here, we present an estimate of the de novo mutation rate in the rhesus macaque (Macaca mula

266 hly accurate pedigree data, we estimated the de novo mutation rate of the horse MSY and showed that v

267 The SLC12A2 de novo mutation rate was demonstrated to be significant

268 are several orders of magnitude higher than de novo mutation rates (1 in 10,000,000 or 100,000,000 b

269 ted number, as determined from gene-specific de novo mutation rates (P = 1.43 x 10(-10)).

270 Resistance was associated with de novo mutations, rather than acquisition of resistant

271 ave implications related to the incidence of de novo mutations relating to maternal age.

272 ilters to discriminate genuine from spurious de novo mutations remains an unsolved challenge.

273 tionally relevant genes with multiple unique de novo mutations revealed four mutations in protein pho

274 of published single-nucleotide variant (SNV) de novo mutations showed evidence consistent with putati

275 ticity proceeded from standing variation and de novo mutations; shown how antagonistic pleiotropy and

276 number of identified X-linked genes in which de novo mutations specifically cause ID in females is li

277 De novo mutation studies also inform population genetics

278 larger than an analogously elevated rate for de novo mutations, suggesting that most rare-variant eff

279 bination is mutagenic: Crossovers carry more de novo mutations than nonrecombinant DNA molecules anal

280 It is usually caused by a de novo mutation that occurs on multiple haplotypes and

281 that roughly 10% of sporadic CHD cases have de novo mutations that contribute significantly to the d

282 explained by the age of the father and that de novo mutations that occur more frequently in the germ

283 We found a high diversity of de novo mutations, the majority of which were undetectab

284 atively high rate of SDY cases stemming from de novo mutations, then the WEMA should become even more

285 findings expand the repertoire of functional de novo mutations to include "functional" synonymous one

286 Pretreatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negativ

287 In genome-wide screening studies for de novo mutations underlying autism and intellectual dis

288 he relative contribution of pre-existing and de novo mutations varies across drug regimens.

289 An additional de novo mutation was found in TAB2 (c.1705G>A, p.Glu569L

290 ssay suggested that each InDel occurred as a de novo mutation, was carried-over from the parental mic

291 ng a series of bioinformatics filters, fetal de novo mutations were detected at a sensitivity of 85%

292 The EIF2B1 de novo mutations were found to map to the same protein

293 Similarly, damaging de novo mutations were identified in genes encoding the

294 MTC is curable in patients with de novo mutations when nonendocrine MEN 2B components ar

295 Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID

296 chondrial disease can be caused by recurrent de novo mutations, which has significant implications fo

297 Here, we combine data on >300,000 human de novo mutations with high-resolution nucleosome maps a

298 De novo mutations with predicted splice-altering consequ

299 fied, several are hit by multiple functional de novo mutations, with RAB2A and SETD1A showing the hig

300 ausal genes by looking for an excess load of de novo mutations within those genes.