|
Genetics Of Amyotrophic Lateral Sclerosis
There are more than 25 genes known to be associated with amyotrophic lateral sclerosis (ALS) as of June 2018, which collectively account for about 70% of cases of familial ALS (fALS) and 10% of cases of sporadic ALS (sALS). About 5–10% of cases of ALS are directly inherited. Overall, first-degree relatives of an individual with ALS have a 1% risk of developing ALS. ALS has an oligogenic mode of inheritance, meaning that mutations in two or more genes are required to cause disease. ''C9orf72'' is the most common gene associated with ALS, causing 40% of familial cases of ALS, as well as a small percentage of sporadic cases; it also causes about 25% of familial cases of frontotemporal dementia. The pathogenic mutation is a hexanucleotide repeat expansion (a series of six nucleotides repeated over and over); the more repeats in ''C9orf72'', the more pathogenic the mutation. People without ALS tend to have fewer than 25 repeat units, while people with ALS due to a mutation in ''C9orf7 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most common type of motor neuron diseases. Early symptoms of ALS include stiff muscles, muscle twitches, and gradual increasing weakness and muscle wasting. ''Limb-onset ALS'' begins with weakness in the arms or legs, while ''bulbar-onset ALS'' begins with difficulty speaking or swallowing. Half of the people with ALS develop at least mild difficulties with thinking and behavior, and about 15% develop frontotemporal dementia. Most people experience pain. The affected muscles are responsible for chewing food, speaking, and walking. Motor neuron loss continues until the ability to eat, speak, move, and finally the ability to breathe is lost. ALS eventually causes paralysis and early death, usually from respiratory failure. Most cases of ALS (a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
OMIM
Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM represented phenotypes; the rest represented genes, many of which were related to known phenotypes. Versions and history OMIM is the online continuation of Dr. Victor A. McKusick's ''Mendelian Inheritance in Man'' (MIM), which was published in 12 editions between 1966 and 1998.McKusick, V. A. ''Mendelian Inheritance in Man. Catalogs of Autosomal Dominant, Autosomal Recessive and X-Linked Phenotypes.'' Baltimore, MD: Johns Hopkins University Press, 1st ed, 1996; 2nd ed, 1969; 3rd ed, 1971; 4th ed, 1975; 5th ed, 1978; 6th ed, 1983; 7th ed, 1986; 8th ed, 1988; 9th ed, 1990; 10th ed, 1992. Nearly all of the 1,486 entries in the first edition of MIM discussed phenotypes. MIM/OMIM is produced and curated at the Johns Hopkins School of Medicine ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ATXN2
Ataxin-2 is a protein that in humans is encoded by the ''ATXN2'' gene. Mutations in ATXN2 cause spinocerebellar ataxia type 2 (SCA2). Protein structure Ataxin-2 contains the following protein domains: * Two LSm domains, which likely allow it to bind RNA * A PAM2 motif, predicted to associate with the poly(A)-binding protein * A polyglutamine tract in some species (located near the amino terminal in primates and between the LSm domains in insects) A potential transcript variant, missing an internal coding exon, has been described; however, its full-length nature is not certain. Species, tissue, and subcellular distribution ''ATXN2'' is conserved across eukaryotes. Most vertebrates have two orthologs of the gene (called ''ATXN2'' and ''ATXN2L'' in humans), with the exception of birds which only have one. Plant species have two to six ''ATXN2'' orthologs. ''ATXN2'' is ubiquitously expressed in different tissues. Within individual cells, it localizes to the Golgi apparatus and st ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Optineurin
Optineurin is a protein that in humans is encoded by the ''OPTN'' gene. Function This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein. OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection. Model organisms Model organisms have been used in the study of OPTN function. A conditional knockout mouse line, called ''Optntm1a(EUCOMM)Wtsi'' was generated as part of t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FIG4
Polyphosphoinositide phosphatase also known as phosphatidylinositol 3,5-bisphosphate 5-phosphatase or SAC domain-containing protein 3 (Sac3) is an enzyme that in humans is encoded by the ''FIG4'' gene. Fig4 is an abbreviation for Factor-Induced Gene. Function Sac3 protein belongs to a family of human phosphoinositide phosphatases containing a Sac1-homology domain. The Sac1 phosphatase domain encompasses approximately 400 amino acids and consists of seven conserved motifs. It harbors the signature CX5R (T/S) catalytic sequence also found in other lipid and protein tyrosine phosphatases. The founding protein, containing this evolutionarily-conserved domain, has been the first gene product isolated in a screen for Suppressors of yeast ACtin mutations and therefore named Sac1. There are 5 human genes containing a Sac1 domain. Three of these genes (gene symbols SACM1L, INPP5F and FIG4), harbor a single Sac1 domain. In the other two genes, synaptojanin 1 and 2, the Sac1 domain coexist ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Angiogenin
Angiogenin (ANG) also known as ribonuclease 5 is a small 123 amino acid protein that in humans is encoded by the ''ANG'' gene. Angiogenin is a potent stimulator of new blood vessels through the process of angiogenesis. Ang hydrolyzes cellular RNA, resulting in modulated levels of protein synthesis and interacts with DNA causing a promoter-like increase in the expression of rRNA. Ang is associated with cancer and neurological disease through angiogenesis and through activating gene expression that suppresses apoptosis. Function Angiogenin is a key protein implicated in angiogenesis in normal and tumor growth. Angiogenin interacts with endothelial and smooth muscle cells resulting in cell migration, invasion, proliferation and formation of tubular structures. Ang binds to actin of both smooth muscle and endothelial cells to form complexes that activate proteolytic cascades which upregulate the production of proteases and plasmin that degrade the laminin and fibronectin layers ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
VAPB
Vesicle-associated membrane protein-associated protein B/C is a protein that in humans is encoded by the ''VAPB'' gene. The VAPB gene is found on the 20th human chromosome. Together with VAPA, it forms the VAP protein family. Function The protein encoded by this gene is a type IV membrane protein found in plasma and intracellular vesicle membranes. The encoded protein is found as a homodimer and as a heterodimer with VAPA. This protein also can interact with VAMP1 and VAMP2 and may be involved in vesicle trafficking. Like VAPA, VAPB binds to proteins that contain a FFAT motif. Considerable interest in VAPB has arisen because mutations in this protein are associated with rare, familial forms of motor neuron disease (also called amyotrophic lateral sclerosis and Lou Gehrig's disease Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SPG11
Spatacsin is a protein that in humans is encoded by the ''SPG11'' gene. Function Spatacsin, in combination with the SPG15 protein, attaches the AP5 adaptor complex to the outside of late Endosomes or Lysosomes when the protein via which it binds is in a particular state. Pathology Mutations of the SPG11 gene cause a rare form of spastic paraplegia Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness ( spasticity) and contraction in the lower limbs. HSP is also known as heredita ..., spastic paraplegia type 11. References Further reading * * * * * External links GeneReviews/NCBI/NIH/UW entry on Spastic Paraplegia Type 11 SPG11-Related Hereditary Spastic Paraplegia with Thin Corpus Callosum {{gene-15-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SETX
Probable helicase senataxin is an enzyme that in humans is encoded by the ''SETX'' gene. This gene encodes a protein named senataxin, a 302kDa protein Sequence and structure There is high homology between human SETX and yeast Sen1. Sen1 in yeast is a RNA/DNA helicase and the highly conserved sequences between these genes, particularly in the helicase domain, indicates that SETX in humans may have similar roles in gene expression and maintaining genome stability. In Sen1, the N-terminus has shown interactions with the C-terminal domain of RNA polymerase II, ribonuclease III, and NER factor Rad2/XPG. Meanwhile, the C-terminus encodes the DNA/RNA helicase activity. Similarly, SETX encodes the senataxin protein that has a N-terminal that is likely to be involved with interacting with other proteins. Senataxin interacts with RNA polymerase II and poly(A) binding proteins. At the C-terminal, senataxin has a DEAD box helicase domain. Function Although senataxin is widely expresse ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ALS2
Alsin is a protein that in humans is encoded by the ''ALS2'' gene. ''ALS2'' orthologs have been identified in all mammals for which complete genome data are available. See also * Juvenile primary lateral sclerosis * Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ... References Further reading * * * * * * * * * * * * * * * * * External links GeneReviews/NCBI/NIH/UW entry on ALS2-Related Disorders OMIM entries on ALS2-Related Disorders * {{gene-2-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Autosomal Recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a mutation in one of the genes, either new (''de novo'') or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes ( autosomes) and their associated traits, while those on sex chromosomes (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child (see Sex linkage). Since there is only one copy of the Y chromosome, Y-linked traits cannot be dominant or recessive. Additionally, there are other forms of dominance such as incomplete d ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Autosomal Dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a mutation in one of the genes, either new (''de novo'') or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes ( autosomes) and their associated traits, while those on sex chromosomes (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child (see Sex linkage). Since there is only one copy of the Y chromosome, Y-linked traits cannot be dominant or recessive. Additionally, there are other forms of dominance such as incomplete d ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
_(14582377398).jpg "Click for more on -> Autosomal Dominant")