ライフサイエンスコーパス: de novo mutation

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

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

3 gene and gene set by calibrating a model of de novo mutation.

4 or HCM or sudden cardiac death, suggesting a de novo mutation.

5 he E42K victim's parental DNA demonstrated a de novo mutation.

6 diversity, both through mixed infection and de novo mutation.

7 either an autosomal recessive disorder or a de novo mutation.

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

9 the variants were demonstrated to represent de novo mutations.

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

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

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

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

14 oach to classify candidates as true or false de novo mutations.

15 5% of NSC is sporadic, suggesting a role for de novo mutations.

16 ios (n = 18) to search for rare inherited or de novo mutations.

17 n identified from rare variation, especially de novo mutations.

18 reproductive fitness, suggesting a role for de novo mutations.

19 ve fitness, pointing to a causative role for de novo mutations.

20 such CNVs must frequently occur as recurrent de novo mutations.

21 l diagnostic yield was 16%, mostly involving de novo mutations.

22 to mood disorders might be most evident for de novo mutations.

23 ose either as ancient founders, or recurrent de novo mutations.

24 Eight patients had de novo mutations.

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

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

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

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

29 We identified 21 de novo mutations, 11 of which were protein altering.

30 which the parents accepted genetic testing; de novo mutations accounted for the other two patient ca

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

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

33 utation in the FDFM family and the recurrent de novo mutation affect residues in different protein do

34 We show that de novo mutations affect genes with diverse functions an

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

36 Inherited and de novo mutations affecting many genes were discovered i

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

38 Here we show that small de novo mutations, affecting one or a few nucleotides, a

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

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

41 from a pre-existing pool rather than through de novo mutation and subsequent population fixation.

42 A total of 10 de novo mutations and 3 X-linked (maternally inherited)

43 The metastasis contained two de novo mutations and a large deletion not present in th

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

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

46 older fathers have an increased risk of both de novo mutations and neuropsychiatric disorders.

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

48 y heterogeneous with a major contribution of de novo mutations and that WES is significantly superior

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

50 De-novo mutations and advanced parental age as a risk fa

51 y, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for K

52 letely or highly attenuated, indicating that de novo mutation, and not selection among quasispecies e

53 eight unrelated individuals who harbour this de novo mutation, and thus define the 'TUBB3 E410K syndr

54 Meiotic recombination and de novo mutation are the two main contributions toward g

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

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

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

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

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

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

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

62 ectrum disorders (ASDs) have identified many de novo mutations but few recurrently disrupted genes.

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

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

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

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

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

68 The same de novo mutation (c.1252C>T, p.R418W) in ADCY5 was found

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

70 3K7, including one highly recurrent (n = 15) de novo mutation (c.1454C>T [ p.Pro485Leu]) proximal to

71 e amino acid (Arg51), and two were identical de novo mutations (c.151C>T [p.Arg51Cys]) in unrelated c

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

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

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

75 with most due to common variation, and rare de novo mutations contribute substantially to individual

76 Including copy number variants, coding de novo mutations contribute to about 30% of all simplex

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

78 ively parallel DNA sequencing has shown that de-novo mutations contribute to approximately 10% of sev

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

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

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

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

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

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

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

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

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

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

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

90 validation, we identified 49 and 35 germline de novo mutations (DNMs) in two trio offspring, as well

91 De novo mutations (DNMs) originating in gametogenesis ar

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

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

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

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

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

97 conserved region of KCNJ2 that resulted in a de novo mutation E299V.

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

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

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

101 Specifically, we built a classifier, named De Novo Mutation Filter (DNMFilter), using gradient boos

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

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

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

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

106 idered to be relevant to discriminating true de novo mutations from artifacts, and then employed a ma

107 We present DeNovoGear software for analyzing de novo mutations from familial and somatic tissue seque

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

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

110 Accurate detection of de novo mutations from sequencing data is a critical ste

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

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

113 18) was very informative, with an excess of de novo mutations identified in genes predicted to be in

114 ic encephalopathies identified an additional de novo mutation in 1 proband with EIMFS.

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

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

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

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

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

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

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

126 phalopathy type 4 (EIEE4) patient carrying a de novo mutation in STXBP1.

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

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

129 rated that all 4 patients had the exact same de novo mutation in the broadly expressed transcription

130 vioral characterization of an ASD-associated de novo mutation in the hDAT.

131 Such alleles arise by de novo mutation in the individual or in recent ancestry

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

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

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

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

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

137 ,133 schizophrenia cases and 9,274 controls, de novo mutations in 1,077 family trios, and copy number

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

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

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

141 We identified 40 de novo mutations in 27 cases affecting 40 genes, includ

142 Additional de novo mutations in 3 of these candidate genes were ide

143 Here we compare the incidence of de novo mutations in 362 severe CHD cases and 264 contro

144 We identified 79 de novo mutations in 53 of 100 patients.

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

146 isrupted in schizophrenia may be revealed by de novo mutations in affected persons from otherwise hea

147 enetic risk factors, we assessed the role of de novo mutations in ALS by sequencing the exomes of 47

148 tic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD

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

150 th high-functioning, idiopathic ASD revealed de novo mutations in at least one of these genes in 6 of

151 highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associate

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

153 ng upstream PI3K-AKT pathway mutations carry de novo mutations in CCND2 (encoding cyclin D2) that are

154 De novo mutations in CHD8 are strongly associated with a

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

156 with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcriptio

157 nodeficiencies with variable penetrance, and de novo mutations in disorders with a severe phenotype h

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

159 We discovered 3 heterozygous de novo mutations in either CALM1 or CALM2, 2 of the 3 h

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

161 how a significant excess of protein-altering de novo mutations in genes expressed in the developing h

162 We find a marked excess of de novo mutations in genes involved in the production, r

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

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

165 may be associated with an increased rate of de novo mutations in germ cells (sperms or eggs), we exa

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

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

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

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

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

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

172 ole-exome sequencing approach, we identified de novo mutations in MLL in five of the six individuals.

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

174 Potentially causative de novo mutations in novel candidate genes were detected

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

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

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

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 We identified de novo mutations in persons with schizophrenia and then

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

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

183 Our analyses suggest a major role for de novo mutations in schizophrenia as well as a large mu

184 fetal development, genes harboring damaging de novo mutations in schizophrenia formed a network sign

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

186 mong ASD probands, we identified deleterious de novo mutations in six of 32 (19%) families and X-link

187 There are also two de novo mutations in SMAD2, which regulates H3K27 methyl

188 Heterozygous de novo mutations in SOX2 have been reported in approxim

189 De novo mutations in specific mTOR pathway genes cause b

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

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

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

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 al profile of sperm as men age, and enriches de novo mutations in the offspring of older fathers that

205 in the paternal germline are associated with de novo mutations in the offspring of older men.

206 D, the contribution of inherited variants or de novo mutations in the setting of CHD has been unclear

207 De novo mutations in the X-linked gene encoding the tran

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

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

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

211 d identified two additional individuals with de novo mutations in this gene.

212 Ten de novo mutations in three previously identified disease

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

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

215 brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a uniq

216 All patients harboured de novo mutations in WDR45, encoding a beta-propeller pr

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

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

219 deletion, and sequencing of HDAC4 identified de novo mutations, including one intragenic deletion pro

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

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

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

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

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

225 (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected beta-ca

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

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

228 ew candidate genes for ASDs and suggest that de novo mutations may contribute substantially to the ge

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

233 ights into the genetic architecture (role of de novo mutations), neurobiological correlates (altered

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

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

236 esistance rapidly emerges, in some cases via de novo mutation of the drug target.

237 an exome-sequencing approach, we identified de novo mutations of KAT6B in five individuals with GPS;

238 ng that these families would be enriched for de novo mutations of major effect.

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

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, enco

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

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

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

245 Our results indicate that de novo mutation or loss of heterozygosity in stromal AP

246 alignment issues, which may either miss true de novo mutations or call too many false ones, making do

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

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

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

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

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

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

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

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

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

256 All were found to carry the same de novo mutation, p.Glu17Lys, in the serine/threonine ki

257 al framework for the analysis of excesses in de novo mutation per gene and gene set by calibrating a

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

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

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

261 De novo mutation plays an important role in autism spect

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

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

264 We identified de novo mutations, previously reported pathogenic mutati

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

266 tion at a relative prevalence reflecting the de novo mutation rate and the distribution of 17p11.2 du

267 population divergences recently suggested by de novo mutation rate estimates in the nuclear genome.

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

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

270 er sequencing of eight single cells revealed de novo mutation rates with distinct characteristics.

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

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

273 ll as a higher prevalence of gene-disruptive de novo mutations relative to controls.

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

275 De novo mutations represent an important cause of intell

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

277 rited variants indicated that the identified de novo mutations show a large excess of non-synonymous

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

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

280 ithin EE genes previously identified through de novo mutation studies.

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

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

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

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

285 In the remaining 29 patients with de novo mutations, the diagnosis of MEN 2B was triggered

286 generation sequencing approaches to identify de novo mutations, the genetic convergence of familial a

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

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

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

290 Nine probands had de novo mutations, two had an affected sibling or parent

291 lex interactions, with resistance arising by de-novo mutation under clinical antibiotic selection or

292 Under the hypothesis that de novo mutations underlie a substantial fraction of the

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

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

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

296 We found that amino acid-altering de novo mutations were enriched in genes encoding chroma

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

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

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.