Fmr1 humans gene contains trinucleotide repeat expansion. Medical search. Frequent questions

Fragile X syndrome (FXS) is the most common inherited cause of human mental retardation. (jneurosci.org)
other mutations involving the FMR1 gene can cause FXS if they prevent production or alter functional domains of the encoded protein, the fragile X mental retardation protein (FMRP) ( O'Donnell and Warren, 2002 ). (jneurosci.org)
Fragile X syndrome (FXS) is caused by expansion of the CGG trinucleotide repeat in the Fragile X Mental Retardation gene, FMR1 . (ny.gov)
Loss of FMR2 gene transcription causes mental retardation. (sdbonline.org)
The expansion of CGG/CCG trinucleotides in the fragile X mental retardation (FMR1) gene leads to Fragile X syndrome (FXS), one of the most common genetic disorders. (ntnu.edu.tw)
Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. (wjgnet.com)
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)

By studying humans, mice, flies and yeast Nelson's research group has characterized the origins of instability in the repeat, the consequences of "premutation" length expansions, and the function of FMR1 and related FXR1 and FXR2. (wikipedia.org)
In this condition, the CGG trinucleotide repeat in the FMR1 gene is repeated about 55 to 200 times, which is referred to as a premutation. (medlineplus.gov)
For unknown reasons, the premutation leads to the overproduction of abnormal FMR1 mRNA that contains the repeat expansion. (medlineplus.gov)
In addition, the repeats make producing protein from the blueprint more difficult, and consequently, some people with the FMR1 gene premutation have lower than normal amounts of FMRP. (medlineplus.gov)
Men, and some women, with an FMR1 gene premutation are at increased risk of developing a disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). (medlineplus.gov)
As in FXPOI (described above), the premutation causes overproduction of abnormal FMR1 mRNA containing the expanded repeat region, and researchers believe that this abnormal mRNA causes FXTAS. (medlineplus.gov)
Family as a Context for Child Development: Mothers with the FMR1 Premutation and Their Children with Fragile X Syndrome. (cdc.gov)
The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. (bvsalud.org)
Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. (bvsalud.org)
Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. (bvsalud.org)
If a homozygous female, premutation, or full mutation is identified or suspected, a second tier of testing consists of Eco RI and Eag I restriction digest followed by Southern blot analysis using the DNA probe, StB12.3 to determine methylation status of the FMR1 gene and approximate number of trinucleotide repeats. (uab.edu)

This was the first to be identified as the underlying mutations in human genetic disorders. (wikipedia.org)
In humans, mutations affecting the genes of this family are associated with specific diseases. (sdbonline.org)
Genetic disorders result from new or inherited gene mutations . (amboss.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)
The genes/mutations could act alone or interact with other genetic and/or epigenetic or environmental factors, causing autism or related disorders. (neurotransmitter.net)
The decision to rescreen a patient should be undertaken only with the guidance of a genetics professional who can best assess the incremental benefit of repeat testing for additional mutations. (acog.org)
21 allelic mutations have been discovered in the APP gene. (findzebra.com)

The DNA Replication Program Is Altered at the FMR1 Locus in Fragile X Embryonic Stem Cells. (ny.gov)
Comprehensive Analysis of Fragile X Syndrome: Full Characterization of the FMR1 Locus by Long-Read Sequencing. (cdc.gov)
Fragile X cases have more than 200 repeats of the trinucleotide CGG at a fragile locus of the X chromosome (Xq27.3) which affords the basis of the molecular diagnosis of the syndrome. (omicsonline.org)
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)

2) lilli mutation strongly suppresses the rough eye phenotype of ectopically expressed phyllopod (Tang, 2001), and (3) lilli was identified in a screen for genes that enhance the embryonic lethal phenotype of dpp alleles (Su, 2001). (sdbonline.org)
All homologous chromosome pairs contain two variant forms of the same gene , called " alleles ," which are passed down from parent to offspring. (amboss.com)
In a population of 250 individuals , there will be a total of 500 gene copies (all individuals carry two alleles of a gene ). (amboss.com)
Maternal FMR1 alleles expansion in newborns during transmission: a prospective cohort study. (cdc.gov)
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)
Individuals with pre-mutation alleles have 59-230 repeats whereas individuals with intermediate sized alleles ("gray zone" alleles) have 41-58 repeats, broadly defined. (uab.edu)

Nelson's molecular techniques led to the development of genome mapping and sequencing and discovery of disease genes, contributing efforts to map and sequence of the human X chromosome. (wikipedia.org)
Dr. Warren used the unusual fragility of the X chromosome in patients with fragile X as a tool to begin the search for the causative gene, a tool that he shared with the other top scientists in the fragile X field. (emory.edu)
Fragile X is usually caused by a trinucleotide expansion in the FMR1 gene on the X chromosome. (uab.edu)

David L. Nelson (born 1956) is an American human geneticist, currently an associate director at the Intellectual and Developmental Disabilities Research Center (1995), and professor at the Department of Molecular and Human Genetics at Baylor College of Medicine BCM since 1999. (wikipedia.org)
Nelson is a member of the Board of Directors of the American Society of Human Genetics, was its President in 2018, and served as Secretary from 2003 to 2009. (wikipedia.org)
Nelson served on the editorial boards of eleven academic journals, including American Journal of Human Genetics, Mammalian Genome, Clinical Genetics (journal), and Genome Research. (wikipedia.org)
Human genetics is the study of the human genome and the transmission of genes from one generation to the next. (amboss.com)

Their findings in FMR1 explained the unusual inheritance in Fragile X syndrome and provided the principles for all subsequent unstable repeat disorders such as myotonic dystrophy, Huntington's disease, and amyotrophic lateral sclerosis. (wikipedia.org)
In 2014, Emory Fragile X Center was funded by NIH entitled "Modifiers of FMR1 -associated disorders: application of high throughput technologies", which enabled us to identify the genetic modifiers for fragile X-associated disorders, including fragile X syndrome, FXTAS, and FXPOI. (emory.edu)
DESCRIPTION (provided by applicant): Expansion of the trinucleotide repeat CGG in the FMR1 gene causes dysregulation of FMR1 protein expression and results in a host of serious conditions, from cognitive impairment, autism, ovarian failure, and progressiveneurological disorders. (sbir.gov)

FMR1 allele frequencies in 51,000 newborns: a large-scale population study in China. (cdc.gov)
Carrier screening is a term used to describe genetic testing that is performed on an individual who does not have any overt phenotype for a genetic disorder but may have one variant allele within a gene(s) associated with a diagnosis. (acog.org)

Trinucleotide repeat expansion in the FMR1 gene is caused by instability in early development and during germ cell production and is thought to be a result of DNA polymerase slippage during DNA replication. (ny.gov)
This lends support to the "origin switch" model of slippage, in which DNA replication through the repeat region increases the formation of secondary structures - when a DNA strand binds to itself rather than the complimentary strand - thereby causing the DNA polymerase to slip and resulting in expansion of the CGG repeats. (ny.gov)
When the CGG triplet fold into the hairpin structure, the new generated CGG repeat would enter the hairpin region and the DNA polymerase won't work. (ntnu.edu.tw)
Polymerase chain reaction analysis is used as a first tier test to define the repeat size. (uab.edu)
Polymerase chain reaction analysis is used to further define the repeat number more precisely. (uab.edu)

Epigenetic regulation of gene expression encompasses mechanisms that allow regulating the expression of the genes without modification of the DNA sequence. (amboss.com)
The overexpansion of CGG repeat would trigger hypermethylation, an abnormal DNA methylation and lead to inhibition of histone modification and epigenetic gene of FMR1 silence. (ntnu.edu.tw)

Normal individuals have CGG repeats ranging from 6 to 54 copies, but FXS patients frequently have over 200 copies, resulting in transcriptional silencing of the gene such that no protein is produced. (ny.gov)
The absence of FMR1 protein causes the characteristics of FXS, but CGG expansion is variable, leading to mosaicism within individuals and the range of characteristics seen in patients. (ny.gov)
The FMR1 gene provides instructions for making a protein called FMRP. (medlineplus.gov)
The lilli gene encodes a nuclear protein related to the AF4/FMR2 family. (sdbonline.org)
This subtype is due to a mutation in the APP gene (21q21.2), encoding the beta-amyloid precursor protein. (findzebra.com)

Human APP mRNA was detected in neurons and neuronal processes, but not in vessel walls. (findzebra.com)

Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. (neurotransmitter.net)
In the present study, genes across the 2q24-q33 interval were analyzed to identify an autism susceptibility gene in this region. (neurotransmitter.net)
CONCLUSIONS: A strong association of autism with SNPs within the SLC25A12 gene was demonstrated. (neurotransmitter.net)

Nelson's work using introduced selectable genes expanded approaches to whole human genome mapping. (wikipedia.org)
The human genome consists of 23 pairs of chromosomes ( 22 pairs of homologous chromosomes and one pair of sex chromosomes ). (amboss.com)
As the technology evolves and test costs decline, whole genome sequencing (WGS), which can assess genetic sequences of nuclear and mitochondrial DNA and copy number variants (CNVs), or whole exome sequencing (WES), which can assess genetic sequences of the coding region of nuclear genes, but usually does not cover mitochondrial DNA and does not consistently identify CNVs, in combination with CMA, may become first-line testing for these conditions. (arupconsult.com)
Although first observed in the 19th century, their structures were not identified until in the 1960s and their presence and fuller relevance in the human genome only clarified in the last few years. (anti-agingfirewalls.com)
Thousands of long non-coding RNA (lncRNA) genes are annotated in the human genome. (biomedcentral.com)

Gene ontology and phenotype-genotype analysis suggested that variants in IGF1 , SYP and LAS1L could plausibly confer risk for ASD. (nature.com)

Beyond Trinucleotide Repeat Expansion in Fragile X Syndrome: Rare Coding and Noncoding Variants in FMR1 and Associated Phenotypes. (cdc.gov)
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)

In 1991, an international team of scientists, led by Dr. Warren, discovered the FMR1 gene and the mechanisms of trinucleotide repeat expansion that caused the fragile X phenotype. (emory.edu)

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)

Nelson's research group has used flies and mice to identify and characterize modifiers that showed that the CGG repeat is necessary and sufficient to affect mammalian neurons. (wikipedia.org)

Now, results published in Molecular Cell from a team led by Drs. Carl Schildkraut and Jeannine Gerhardt, at the Albert Einstein College of Medicine, examined DNA replication and the use of DNA origins of replication in normal and FXS human embryonic stem cells (hESCs). (ny.gov)
This is the first study to examine FXS and trinucleotide repeat expansion in human embryonic stem cells. (ny.gov)
These mutant phenotypes correlate with markedly reduced expression of the early zygotic genes serendipity alpha , fushi tarazu and huckebein , which are essential for cellularization and embryonic patterning (Tang, 2001). (sdbonline.org)

These results suggest that transcriptional elongation control is especially important for rapidly expressed genes to support digestion and metabolism, many of which have sex-biased function. (sdbonline.org)

With a group of international collaborators, Nelson's research group was able to identify a recurrent, homology-driven deletion in the NEMO gene in Incontinentia pigmenti (IP), an X-linked genetic disease. (wikipedia.org)
Each human cell contains 23 pairs of homologous chromosomes (corresponding in structure and genetic information, i.e., 23 chromosomes are inherited from each parent). (amboss.com)

Nelson and other collaborators at BMC, Emory University, and Erasmus University Rotterdam identified a massive expansion of CGG repeat (Trinucleotide repeat disorder) in FMR1. (wikipedia.org)

Nelson contributed to the human, mouse and fly reference sequences and was a co-discoverer of the mutation that causes Fragile X syndrome as an expansion of a trinucleotide repeat in the FMR1 gene. (wikipedia.org)
Almost all cases of fragile X syndrome are caused by an expansion of the CGG trinucleotide repeat in the FMR1 gene. (medlineplus.gov)
The usual cause of the fragile X syndrome is an expanded (CGG)n repeat in the 5-prime noncoding region of the FMR1 gene. (coriell.org)

Their research results are being used in research to define the role of FMR1 in development and potential treatment for these diseases in adulthood. (wikipedia.org)
We now know those structures are very relevant to many critical biological processes like gene regulation, expression of telomerase and telomere maintenance, understanding of growth/oncogenes like C-myc, understanding of organismic development, comprehension of certain enigmatic diseases like ALS and possible new cancer treatments. (anti-agingfirewalls.com)
However, how lncRNAs contribute to the development of hereditary diseases in human is still mostly unknown. (biomedcentral.com)

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)

Applying PCR, a technique that allows rapid gene mapping and isolation of specific chromosomal regions, Nelson et al. (wikipedia.org)

In contrast, healthy individuals show that AGG/CCT interruptions exist in every 9-10 CGG/CCG trinucleotides. (ntnu.edu.tw)

This CGG repeat segment is typically interrupted several times by a different three-base sequence, AGG. (medlineplus.gov)
On the other hand, MALAT1 whose sequence is highly conserved between human and mice do not tend to be conserved on the functional level. (biomedcentral.com)

One region of the FMR1 gene contains a particular DNA segment known as a CGG trinucleotide repeat, so called because this segment of three DNA building blocks (nucleotides) is repeated multiple times within the gene. (medlineplus.gov)

In these cases, CGG is abnormally repeated more than 200 times, which makes this region of the gene unstable. (medlineplus.gov)
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)

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)

Nelson and his research group have defined roles for FMR1 and paralogs in circadian rhythm, energy metabolism, neuronal stem cell development, and microRNA function. (wikipedia.org)

Fmr1 KO mice exhibit hyperactivity in open field tests, heightened seizure susceptibility, exaggerated responses to sensory stimulation, normal fear conditioning, and mild impairments in spatial learning tasks ( Kooy, 2003 ). (jneurosci.org)
On the other hand, Li and colleagues ( 2002 ) found that synaptic potentials recorded in layer IV/V of frontal neocortex in response to white matter stimulation showed greatly diminished LTP in Fmr1 KO mice. (jneurosci.org)
We find that LTP of monosynaptic responses evoked by selective stimulation of excitatory associational fibers is substantially reduced in slices of anterior piriform cortex (APC) from Fmr1 KO mice, compared with wild-type (WT) controls. (jneurosci.org)
Knockdown experiments on human and mice lung cancer cell lines showed a decrease migration and metastatic rate in human. (biomedcentral.com)

16 repeat units) CGG sequences. (ntnu.edu.tw)

Having AGG scattered among the CGG triplets appears to help stabilize the long repeated segment. (medlineplus.gov)

Previous studies have shown that 5% to 15% of patients with ASD have inherited copy number variations (CNVs) or de novo CNVs in some affected genes with synaptic function 10 . (nature.com)

The number of CGG tract is in between 5 and 44 tandem repeat units in the healthy humans, while in the pathological samples, more than 200 repeat units were found in FMR1 gene. (ntnu.edu.tw)

Using a method called SMARD, for single-molecule analysis of replicated DNA, the team observed that FXS hESCs use a different origin of replication, changing the direction of DNA replication through the FMR1 gene, than normal hESCs. (ny.gov)
Once the DNA replication restart, it'll cause the DNA expansion. (ntnu.edu.tw)

We use single-molecule fluorescence resonance energy transfer (smFRET) spectroscopy to study the conformation of CGG repeat with and without the interruption by AGG insertions. (ntnu.edu.tw)
Based on the DNA expansion model from our previous study, we propose a structure and structural dynamics role of AGG insertion in DNA preventing expansion. (ntnu.edu.tw)
The establishment of in vitro naive human pluripotent stem cell cultures opened new perspectives for the study of early events in human development. (bvsalud.org)
Our study opens new perspectives for future applications of naive hiPSCs to study critical stages of human development in 3D starting from a single cell. (bvsalud.org)

Human cellular reprogramming to induced pluripotency is still an inefficient process, which has hindered studying the role of critical intermediate stages. (bvsalud.org)
METHOD: Mutation screening of positional candidate genes was performed in two stages. (neurotransmitter.net)

Almost half of the genes expressed in adults showed reduced expression, supporting a broad role for the three tested genes in steady-state transcript abundance. (sdbonline.org)
The role of several transcription factors and signaling pathways have been characterized during maintenance of human naive pluripotency. (bvsalud.org)

Translocations between MLL (a human trithorax -related gene) and AF4 or AF5q31 are involved in acute lymphoblastic leukemia (Wittwer, 2001, Tang, 2001 and Su, 2001). (sdbonline.org)

Here, we find that persistent mtDNA stress is not associated with basally activated NF-κB signalling or interferon gene expression typical of an acute antiviral response. (regenerativemedicine.net)

Heat can affect their coming and going, and their presence near promoter elements can block gene activation. (anti-agingfirewalls.com)

From 1984 to 1985, in an intramural National Institutes of Health program at the laboratory of Robert Lazzarini, Nelson studied neuroscience and defined genes encoding neurofilament proteins. (wikipedia.org)

CGG repeat can fold into hairpin-like structures or G-quadruplexes, which are still under debating. (ntnu.edu.tw)

Our data suggest that human cellular reprogramming is a transcription factor-driven process that it is deeply dependent on extracellular context and cell population determinants. (bvsalud.org)

Genes showing reduced expression due to these RNAi treatments were short and enriched for genes encoding metabolic or enzymatic functions. (sdbonline.org)
Hundreds of genes were observed with sex-biased differential expression following treatment. (sdbonline.org)
We showed previously that cytoplasmic release of mtDNA activates the cGAS STING TBK1 pathway resulting in interferon-stimulated gene (ISG) expression that promotes antiviral immunity4. (regenerativemedicine.net)

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