Huntington'sInstabilityGenomicGenomesHaplotypesWhole-genomeChromosomeGenomeAllelesTandemPolymorphismPathogenicChromosomalCandidate genesPopulationsNeurodegenerativeNeurologicalSequenceNucleotideFragile X syndroLociProteinsMethylationLectureEpigeneticDeletionsEncodesVariantsDisordersOccur in the codingMechanismsDefectsGeneticsTherapiesPrematureNuclearDiversityRegulationResultOnsetAtaxiaDosagePointRegionDifferentialTypesFoundShowSingleParent
Huntington's3
- For instance, if you've got a mutation caused by triplet repeat expansion, for instance in the Huntington's gene, where the trinucleotide repeats a CAG, you might have 17 CAGs in a normal chromosome. (hstalks.com)
- REVIEW-ARTICLE Intermediate alleles of Huntington's disease HTT gene in different populations worldwide: a systematic review. (geneticsmr.com)
- Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by a dynamic mutation due to the expansion of CAG repeats in the HTT gene (4p16.3). (geneticsmr.com)
Instability1
- The chromosomal instability resulting from this trinucleotide expansion presents clinically as intellectual disability, distinctive facial features, and macroorchidism in males. (wikipedia.org)
Genomic2
- The mechanisms by which genetic variants result in loss of protein function are many and variable, and include large-scale genomic deletions that can involve multiple genes, down to smaller single-exon deletions that may result in the protein reading frame being shifted and a truncated protein, or an in-frame loss of protein sequence. (hstalks.com)
- To profile genomic and epigenomic of a naïve Chinese non-small cell lung cancer (NSCLC) cohort and investigate the association between tumor mutation burden (TMB) and DNA methylation (DNAm) to explore potential alternative/complimentary biomarkers for NSCLC immunotherapies. (biomedcentral.com)
Genomes2
- Trinucleotide repeats are a subset of a larger class of unstable microsatellite repeats that occur throughout all genomes. (wikipedia.org)
- of tandem repeats within their genomes [6, 17]. (scirp.org)
Haplotypes2
- Sequencing of their polymerase chain reaction (PCR) products revealed a G-->A transition immediately preceding the trinucleotide repeats, hence defining 8 distinct haplotypes and 36 possible genotypes. (scite.ai)
- Indeed, mutation detection enhancement gel electrophoresis of mixed PCR products from cloned haplotypes revealed 24 distinct heteroduplex patterns for the six possible trinucleotide heterozygotes. (scite.ai)
Whole-genome2
- To estimate the genome-wide pattern of mutations at STR loci, we analyze blood-derived whole-genome sequencing data for 544 individuals from 29 three-generation CEPH pedigrees. (biomedcentral.com)
- New technologies such as next-generation sequencing (including whole exome or whole genome sequencing) are expanding testing options, discovering new mutations, and creating challenges in counseling, interpreting, and reporting results to the patient. (medlink.com)
Chromosome4
- The first trinucleotide repeat disease to be identified was fragile X syndrome, which has since been mapped to the long arm of the X chromosome. (wikipedia.org)
- The second DNA-triplet repeat disease, fragile X-E syndrome, was also identified on the X chromosome, but was found to be the result of an expanded CCG repeat. (wikipedia.org)
- But in a diseased chromosome, you might have 40 successive copies of CAG trinucleotides in the gene. (hstalks.com)
- Etiology HCHWA-D is due to a mutation in the APP gene on chromosome 21q21.2, encoding the beta-amyloid precursor protein. (findzebra.com)
Genome6
- Many regions of the genome (exons, introns, intergenic regions) normally contain trinucleotide sequences, or repeated sequences of one particular nucleotide, or sequences of 2, 4, 5 or 6 nucleotides. (wikipedia.org)
- Short tandem repeats (STRs) compose approximately 3% of the genome, and mutations at STR loci have been linked to dozens of human diseases including amyotrophic lateral sclerosis, Friedreich ataxia, Huntington disease, and fragile X syndrome. (biomedcentral.com)
- Improving our understanding of these mutations would increase our knowledge of the mutational dynamics of the genome and may uncover additional loci that contribute to disease. (biomedcentral.com)
- Approximately 30% of new STR mutations occur within Alu elements, which compose only 11% of the genome, but only 10% are found in LINE-1 insertions, which compose 17% of the genome. (biomedcentral.com)
- We estimate the average number of de novo genome-wide STR mutations per individual to be approximately 85, which is similar to the average number of observed de novo single nucleotide variants. (biomedcentral.com)
- Some of these tools are designed to detect STR expansions at disease-related loci, while others detect expansions and contractions of STRs genome-wide but are constrained by sequencing read length and the STR motif size. (biomedcentral.com)
Alleles4
- Size variation was readily detected, with four common alleles containing 12-15 repeats. (scite.ai)
- One individual was found to carry a 12 kb deletion in one copy of the ASPA gene on 17p13, which when mutated in both alleles leads to Canavan disease. (biomedcentral.com)
- The considered normal alleles have less than 27 CAG repeats. (geneticsmr.com)
- Intermediate alleles (IAs) show 27 to 35 CAG repeats and expanded alleles have more than 35 repeats. (geneticsmr.com)
Tandem2
- We searched the expressed sequence tag databank for reiterated trinucleotides and selected EST00493 (D2S196E) with 14 tandem ACA triplets as a potentially polymorphic locus. (scite.ai)
- Short tandem repeats (STRs), or microsatellites, are 1-6 base pair (bp) motifs of repeating units of DNA. (biomedcentral.com)
Polymorphism1
- Apolipoprotein E (ApoE) is one of the most extensively studied genes in the context of aging, but there are few population-based studies on ApoE polymorphism in the elderly in developing countries. (scite.ai)
Pathogenic3
- In this second type of disorder, large repeat expansions in DNA are transcribed into pathogenic RNAs that form nuclear RNA foci. (wikipedia.org)
- The third main category of trinucleotide repeat disorders and related microsatellite disorders is due to the translation of repeat sequenced into pathogenic proteins containing a stretch of repeated amino acids. (wikipedia.org)
- Looking at loss-of-function variants and their role in human disease, in fact the majority of rare genetic disorders described to date result from loss-of-function pathogenic variants, that may partially or completely inactivate the gene product. (hstalks.com)
Chromosomal1
- This review emphasizes the potential of analysing chromosomal rearrangements as a means to rapidly define candidate disease loci for further investigation. (neurotransmitter.net)
Candidate genes3
- Next-generation sequencing of the whole exome is useful for testing for multiple candidate genes simultaneously or for discovering new, rare disorders. (medlink.com)
- METHOD: Mutation screening of positional candidate genes was performed in two stages. (neurotransmitter.net)
- The first stage involved identifying, in unrelated subjects showing linkage to 2q24-q33, genetic variants in exons and flanking sequence within candidate genes and comparing the frequency of the variants between autistic and unrelated nonautistic subjects. (neurotransmitter.net)
Populations3
- These populations originated from a common ancestor, and a rapid demographic expansion began approximately 90,000 years ago. (biomedcentral.com)
- The natural populations from China with specific genetic characteristics enriched the gene pools of global A. thaliana collections. (biomedcentral.com)
- We hypothesize that there might be at least three types of autism susceptibility genes/mutations that can be (i) specific to an individual patient or family, (ii) in a genetically isolated sub-population and (iii) a common factor shared amongst different populations. (neurotransmitter.net)
Neurodegenerative1
- The other key point of the slide is to show that these diseases are typically either neurological, neurodegenerative, or neuromuscular. (hstalks.com)
Neurological2
- Trinucleotide repeat disorders, also known as microsatellite expansion diseases, are a set of over 50 genetic disorders caused by trinucleotide repeat expansion, a kind of mutation in which repeats of three nucleotides (trinucleotide repeats) increase in copy numbers until they cross a threshold above which they cause developmental, neurological or neuromuscular disorders. (wikipedia.org)
- Long expansions of transcribed trinucleotide microsatellites have been etiologically associated with some neurological diseases. (scite.ai)
Sequence4
- However, the frequency of occurrence of any one particular repeat sequence disorder varies greatly by ethnic group and geographic location. (wikipedia.org)
- Sometimes, a person may have more than the usual number of copies of a repeat sequence associated with a gene, but not enough to alter the function of that gene. (wikipedia.org)
- The observation of heteroduplex patterns in non-denaturing polyacrylamide gel electrophoresis (instead of the more commonly used denaturing gels) can thus be utilized to increase the informativeness of microsatellite polymorphisms by unraveling otherwise cryptic sequence variation. (scite.ai)
- Diversity and genetic stability in banana genotypes in a breeding program using inter simple sequence repeats (ISSR) markers. (geneticsmr.com)
Nucleotide1
- Two single nucleotide polymorphisms (SNPs) that showed evidence for divergent distribution between autistic and nonautistic subjects were identified, both within SLC25A12, a gene encoding the mitochondrial aspartate/glutamate carrier (AGC1). (neurotransmitter.net)
Fragile X syndro1
- Patients carry from 230 to 4000 CGG repeats in the gene that causes fragile X syndrome, while unaffected individuals have up to 50 repeats and carriers of the disease have 60 to 230 repeats. (wikipedia.org)
Loci2
- Analyzing approximately 1.6 million STR loci, we estimate the empirical de novo STR mutation rate to be 5.24 × 10 −5 mutations per locus per generation. (biomedcentral.com)
- It is possible that each of these mechanisms contributes to the high mutation rate of STRs, but strand slippage is the mechanism proposed for generating most observed mutations in STR loci [ 19 ]. (biomedcentral.com)
Proteins2
- Smaller genetic variants (such as nonsense and frameshift mutations that result in a premature stop codon) can result in disease by producing proteins that lack key functional domains, or they may result in nonsense-mediated mRNA decay, so that no protein is produced from the mutated allele. (hstalks.com)
- Splicing mutations may, like exonic deletions, result in truncated proteins or proteins in which specific residues are deleted. (hstalks.com)
Methylation2
- These repeats are able to promote localized DNA epigenetic changes such as methylation of cytosines. (wikipedia.org)
- There is often increased methylation at CpG islands near the repeat region, resulting in a closed chromatin state, causing gene downregulation. (wikipedia.org)
Lecture2
- I'm going to give a lecture on the mechanisms of human genetic disease. (hstalks.com)
- The aim of this lecture is to provide selected examples of the links between different types of genetic and epigenetic alterations, and the diversity of ways in which they can impact protein function and lead to human genetic disease. (hstalks.com)
Epigenetic3
- The epigenetic alterations and their effects are described more fully by Barbé and Finkbeiner These authors cite evidence that the age at which an individual begins to experience symptoms, as well as the severity of disease, is determined both by the size of the repeat and the epigenetic state within the repeat and around the repeat. (wikipedia.org)
- The genes/mutations could act alone or interact with other genetic and/or epigenetic or environmental factors, causing autism or related disorders. (neurotransmitter.net)
- Change in the epigenetic profile of a cell definitely links the condition with some disease or abnormality. (geneticeducation.co.in)
Deletions1
- Whole exome sequencing is not suitable for detecting polynucleotide repeat disorders or large insertion/deletions. (medlink.com)
Encodes2
- These guarantee onset of early-onset familial Alzheimer disease and all occur in the region of the APP gene that encodes the Aβ domain. (findzebra.com)
- The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase. (lookformedical.com)
Variants1
- Two subjects showed partial duplication of the TM4SF2 gene on Xp11.4, previously implicated in X-linked non-specific mental retardation, but in our subsequent analyses such variants were also found in controls. (biomedcentral.com)
Disorders6
- Trinucleotide repeat disorders and the related microsatellite repeat disorders affect about 1 in 3,000 people worldwide. (wikipedia.org)
- Three categories of trinucleotide repeat disorders and related microsatellite (4, 5, or 6 repeats) disorders are described by Boivin and Charlet-Berguerand. (wikipedia.org)
- The second main category of trinucleotide repeat disorders and related microsatellite disorders involves a toxic RNA gain of function mechanism. (wikipedia.org)
- These disorders have in common that the associated genetic alterations result, in most cases, in altered expression or function of the protein product of the relevant gene, which then directly or indirectly leads to pathophysiological changes that result in disease. (hstalks.com)
- Given that there are thousands of rare genetic disorders, it is of course not possible to provide a detailed comprehensive overview of the molecular mechanisms of all types of human genetic disease, but I hope that the selected examples will provide some insights into this topic. (hstalks.com)
- Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging. (lookformedical.com)
Occur in the coding1
- Some occur in the coding region of the gene, others occur in the five prime region and others occur in the three prime region, and these have different consequences on the function of the gene and the results of the mutation. (hstalks.com)
Mechanisms2
- This results in, variously, a toxic gain of function, a loss of function, a dominant negative effect and/or a mix of these mechanisms for the protein hosting the expansion. (wikipedia.org)
- Translation of these repeat expansions occurs mostly through two mechanisms. (wikipedia.org)
Defects2
- This, in turn, causes multiple RNA processing defects that lead to the diverse clinical manifestations of these diseases. (wikipedia.org)
- An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. (lookformedical.com)
Genetics2
- The focus of my talk is going to be on the genetics of these diseases, and I'll talk very little about the functional biology of these conditions. (hstalks.com)
- 2003) reviewed the pathology and genetics of APP -related CAA and discussed the different neuropathologic consequences of different APP mutations. (findzebra.com)
Therapies1
- Tumor mutation burden (TMB) has been proved to be effective in differentiating responding population of ICI therapies in multiple clinical studies. (biomedcentral.com)
Premature1
- An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease. (lookformedical.com)
Nuclear1
- YBM12-A and YBM12-B). This mutation in leaf color is controlled by a single dominant nuclear gene. (geneticsmr.com)
Diversity1
- Phylogeography and population structure analysis reveals diversity by mutations in Lasiodiplodia theobromae with distinct sources of selection. (geneticsmr.com)
Regulation1
- Epigenetics broadly is a heritable genetic characteristic that is a cell-specific gene expression and regulation achieved by the interaction between DNA and transcriptional factors. (geneticeducation.co.in)
Result2
- These diseases are all caused by microsatellite mutations, where a microsatellite either has three bases, four bases, five bases, or six bases, and these mutations result in excess numbers of copy of these particular units. (hstalks.com)
- Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. (lookformedical.com)
Onset1
- In general, the larger the expansion the faster the onset of disease, and the more severe the disease becomes. (wikipedia.org)
Ataxia1
- The differential diagnosis for the patient may include both genetic and non-genetic possibilities (for example, ataxia, dementia, and Parkinson disease). (medlink.com)
Dosage1
- The results in PAR1/PAR2 are the first large-scale studies of gene dosage in these regions, and the findings at the ASMT locus indicate that further studies of the duplication of the ASMT gene are needed in order to gain insight into its potential involvement in ASD. (biomedcentral.com)
Point2
- the background rate of point mutations [2]. (scirp.org)
- When a point mutation either D10A or H849A is inserted into either domain, it becomes catalytically inactive but still, DNA domains do their work finely that are utilized for various purposes. (geneticeducation.co.in)
Region3
- The first main category these authors discuss is repeat expansions located within the promoter region of a gene or located close to, but upstream of, a promoter region of a gene. (wikipedia.org)
- A partial duplication in the ASMT gene, located in the pseudoautosomal region 1 (PAR1) of the sex chromosomes and previously suggested to be involved in ASD susceptibility, was observed in 6-7% of the cases but in only 2% of controls (P = 0.003). (biomedcentral.com)
- In the present study, genes across the 2q24-q33 interval were analyzed to identify an autism susceptibility gene in this region. (neurotransmitter.net)
Differential1
- Relatively high TMB group ( n = 16, 7.5-13.9 mutations/Mb) harbors more differential DMPs while less in relatively low TMB group ( n = 13, 1.1-2.4 mutations/Mb). (biomedcentral.com)
Types1
- What this slide shows is that these types of mutations can occur in various parts of the gene. (hstalks.com)
Found1
- Negative association findings and research involving the serotonin transporter gene, FMR1, RELN, WNT2, HOXA1, and HOXB1 genes may be found elsewhere on this site . (neurotransmitter.net)
Show1
- In addition, 437 genes show DNAm aberrance status in high TMB patient group and 99 have been reported as its association with lung cancer. (biomedcentral.com)
Parent1
- Phasing these mutations to the parent of origin shows that parental transmission biases vary among families. (biomedcentral.com)