Genetics

[kim]

I was going to post this under the "tumor" thread, but it seems like a large enough topic for it's own.

 

If anyone else is interested in posting here, this is a site where you can hunt down chromosomes and gene locatons.

 

http://www.ncbi.nlm.nih.gov/sites/entrez?c...ood%20Disorders

 

If you have a condition that runs in your family and you have wondered if it's related, just do a search with the word chromosome or gene in it, and see what comes up. I'll post the studies that I have saved, that mention TS and related conditions where they have identified different genes too.

 

 

Here is a TS study linking chromosome 8 (I'll be adding more to this with an edit)

 

http://www.springerlink.com/content/rwhvh6x0xgnra10e

 

We describe here two unrelated families wherein balanced t(6;8) chromosomal translocations occur in individuals diagnosed with TS. In one of these families, the transmission of the translocation is associated with learning and behavioral difficulties; in the other family, one parent is unaffected and the other cannot be traced, thus transmission cannot be demonstrated and it is possible that the translocation may have occurred de novo. The breakpoint on chromosome 8 occurs within the q13 band in both families, suggesting that a gene or genes in this region might contribute to the TS phenotype. Existing linkage and cytogenetic data, suggesting involvement of chromosome 8 in TS families and individuals, further support this hypothesis. We have identified two YAC clones mapping distal and proximal to the chromosome 8 translocation

 

http://www.nanosphere.us/VerigeneMTHFRNucl...stIVD_4468.aspx

 

The MTHFR gene, located on human chromosome 1p36.3, encodes an enzyme that catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, the primary circulating form of folate. This substrate is vital for both DNA synthesis1 and the methionione synthase-catalyzed conversion of homocysteine to methionine.

 

http://ghr.nlm.nih.gov/gene=f5

 

Where is the F5 gene located?

Cytogenetic Location: 1q23

 

How are changes in the F5 gene related to health conditions?

factor V Leiden thrombophilia - caused by mutations in the F5 gene

A specific mutation in the F5 gene is responsible for factor V Leiden thrombophilia

 

 

Recently Published Study (2008) (i have psoriasis or as I fondly refer to it; my dragon elbow) That 1q 24 is interesting inlight of the 1q23 involved in the V Leiden info we have from the other thread. The crohn's info for someone we all know and luv! I also have a friend on another site with TS and his Mom has crohn's.

 

http://www.ihop-net.org/UniPub/iHOP/pm/127...p;pmid=17993580

 

Psoriasis is associated with pleiotropic susceptibility loci identified in type II diabetes and Crohn disease.

 

The analysis of 1256 patients and 2938 unrelated controls found significant associations for loci mapping to chromosomes 1q24 (rs12035082, p = 0.009), 6p22

(rs6908425, p = 0.00015) and 21q22 (rs2836754, p = 0.0003). Notably, the marker showing the strongest phenotypic effect (rs6908425) maps to CDKAL1, a gene also associated with type 2 diabetes. CONCLUSIONS: These results substantiate emerging evidence for a pleiotropic role for s genes that contribute to the pathogenesis of immune-mediated disorders.

[kim]

Very adverse drug reactions have been discussed here. One remark was regarding a poster's mom, who is dealing with Parkinson's.

 

I wanted to mention that thimerosal has been mentioned as screwing up sulfur pathways in many articles. Anytime you see the word thiol or mercaptan, you know they are talking about a pathway that detoxing mercury would be important/associated with.

 

http://en.wikipedia.org/wiki/Thiol

 

In organic chemistry, a thiol is a compound that contains the functional group composed of a sulfur atom and a hydrogen atom (-SH). Being the sulfur analogue of an alcohol group (-OH), this functional group is referred to either as a thiol group or a sulfhydryl group. More traditionally, thiols are often referred to as mercaptans.

 

The term mercaptan comes from the Latin mercurius captans, meaning 'laying hold of mercury,' because the –SH group binds tightly to the element mercury.

 

 

http://gut.bmj.com/cgi/content/abstract/52/4/547

 

Conclusions: Microsomal epoxide hydrolase may play a role in the pathophysiology of Crohn’s disease. Furthermore, the epoxide hydrolase gene is located on chromosome 1q, close to a region previously linked to Crohn’s disease.

 

http://en.wikipedia.org/wiki/Epoxide_hydrolase

 

Epoxide hydrolase (also known as Epoxide hydratase) functions in detoxication during drug metabolism. It converts epoxides from the degradation of aromatic compounds to trans-dihydrodiols which can be conjugated and excreted from the body.

 

Epoxides are significant as cytochrome P450 oxidase metabolites of unsaturated carbon-carbon bonds, but are also mutagenic. Epoxide hydrolase is present in large quantity on endoplasmic reticulum.

 

 

http://gut.bmj.com/cgi/content/abstract/47/2/206?ck=nck

 

BACKGROUND Luminal anionic sulphide may contribute to epithelial damage in ulcerative colitis. Thiol methyltransferase (TMT) governs sulphide detoxification by the colonic mucosa and circulating erythrocytes.

AIMSTo measure levels of TMT activity in erythrocytes of surgically treated cases of colitis or in rectal biopsies of defined groups of colitis.

PATIENTSVenepuncture blood was obtained from 37 blood donors and 27 subjects who had previously undergone a proctocolectomy for colitis: 18 for ulcerative colitis and nine for Crohn's colitis. Rectal biopsies from 122 cases were obtained: 47 without mucosal disease, 33 post-colon resection for cancer, 14 with moderate to severe ulcerative colitis, 15 with quiescent ulcerative colitis, seven with acute Crohn's colitis, and six with radiation proctitis.

METHODSTMT activity was measured by high performance liquid chromatography with radioactive detection to measure 14C methylmercaptoethanol formation, the reaction product of cell extracts incubated with mercaptoethanol and 14C S-adenosylmethionine.

RESULTS Erythrocyte TMT activity of surgically treated cases of colitis was significantly elevated (p<0.001) compared with control cases. TMT activity of rectal biopsies was significantly decreased (p<0.02) in acute but not quiescent ulcerative colitis, Crohn's colitis, or radiation colitis.

CONCLUSIONS Erythrocyte TMT activity was persistently elevated after proctocolectomy for Crohn's disease and ulcerative colitis. No primary defect of TMT activity was found in any case of unoperated colitis but mucosal activity was diminished with disease progression of ulcerative colitis. Studies of genetic control of TMT activity of erythrocytes in inflammatory bowel disease appear worthwhile.

 

 

Keywords: thiol methyltransferase; hydrogen sulphide; methylation; ulcerative colitis; Crohn's disease

[kim]

http://brain.oxfordjournals.org/cgi/conten...30/9/2302?rss=1

 

Novel locus for benign hereditary chorea with adult onset maps to chromosome 8q21.3–q23.3

 

Also, i have read a few posts here regarding seizures. I wanted to post this as there are quite a few area's of this chromosome that look to be seizure related

in that 8q region.

 

http://www.genecards.org/cgi-bin/listdisea...om&search=8 (oops edit to include link to page)

 

In light of the info in the PANDAS study on the other thread about the "suspected pyruvate autoantigen" I thought it was interesting to see

 

8q22.1 Pyruvate dehydrogenase phosphatase deficiency [MIM:608782]

[jewels]

Hi Kim

 

I always love your posts as they always get me thinking round corners.

 

Dh and myself come from a family mixed with a gene pool of various conditions. You have really got me thinking. Do you think we could start an on-line survey of family medical conditions, and see if any conditions or groups of conditions flag up. I am wondering if some children can be more predisposed due to genetics.

 

Just our close family members have Lupus, MS, diabetes, asthma, to name but a few.

 

Do you think this would be a good idea to see if there is a common link?

 

Jules

 

PS I keep guessing about your profession, and I'm now guessing that you're a Doctor.

[Chemar]

 

well, it\'s no secret that I firmly believe in the genetic predisposition link........

 

tho just like at college,I glaze over trying to understand the nitty gritty of genetics beyond the basics........ so thanks Kim for this thread

[kim]

Jewels/Chemar,

 

Thank you guys for making me feel a little less foolish for undertaking something I probably have no business doing! Jules, please, please, never confuse me for someone who has any medical knowledge. I have absolutely none. I hold two state licenses, and they don't require the skills of a rocket scientist, believe me! Jewels any commonalities that you can kick up, would be great.

 

I wanted to drop this on this thread. This Eph2/syndecan thing is something that I have done no reading on, but it is part of the research that I posted on another thread, and I thought it was interesting that the gene appears to be in the same region as the MTHFR.

 

http://www.burnham.org/print.asp?contentID=196

 

EphB2/syndecan-2 signaling in dendritic spine development

Dendritic spines are small protrusions on the surface of dendrites that receive the vast majority of excitatory synapses.

 

and

 

In a subsequent study, we demonstrated that syndecan-2 is phosphorylated on two tyrosine residues by EphB2, a receptor tyrosine kinase that is also concentrated in dendritic spines. Syndecan-2 and EphB2 associate to form a complex in neurons and in the brain. Phosphorylation by EphB2 is necessary for syndecan-2 to associate with EphB2 and to induce dendritic spine formation in cultured neurons.

 

 

http://genome-www.stanford.edu/cgi-bin/gen...p.pl?gene=EPHB2

 

Entrez Gene cytogenetic band: 1p36.1-p35 Ensembl cytogenetic band: 1p36.12 HGNC cytogenetic band: 1p36.1-p35

 

 

 

http://www.nanosphere.us/VerigeneMTHFRNucl...stIVD_4468.aspx

 

The MTHFR gene, located on human chromosome 1p36.3, encodes an enzyme that catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, the primary circulating form of folate. This substrate is vital for both DNA synthesis1 and the methionione synthase-catalyzed conversion of homocysteine to methionine.

[kim]

Cheri,

 

I ran across this today. think this is the the study that was referred to in the other article?

 

 

http://www.accessmylibrary.com/coms2/summa...86-22839413_ITM

 

Genetic polymorphisms in biotranstormation enzymes in Crohn's disease: association with microsomal epoxide hydrolase. (Inflammatory Bowel Disease).

 

Aim: To assess the association of Crohn's disease with genetic polymorphisms in cytochrome P450 lAl, glutathione S-transferases mu-1, pi-1, and theta-1, and epoxide hydrolase.

[kim]

This is dated 2003 but has lots of chromosome linkage

 

http://64.233.167.104/search?q=cache:V16i6...;cd=1&gl=us

 

Of additional interest is linkage of autism and Tourette syndrome to 4p16.3-16.1. This region was recently genetically linked to SLE patients having neuropsychiatric manifestations that, like Tourette syndrome [67], have been associated with antiphospholipid antibodies [97]. Immune influence on neuronal development is well established. Families of cytokines, chemokines, signal transduction molecules, molecules of cell-cell contact, as well as developmental regulatory molecules originally characterized in the immune system have pleiotropic and overlapping functional effects on the developing immune system and the developing brain.

[kim]

Crohn's Gene

 

http://www.blackwell-synergy.com/doi/abs/1...41.2007.01661.x

 

The American Journal of Gastroenterology

Volume 103 Issue 3 Page 615-620, March 2008

 

 

CONCLUSIONS: Our findings confirm recently reported genome-wide associations between the IL-23R gene and CD. They suggest that the gene is also associated with pediatric-onset CD among Canadian children.

 

A genome-wide association study identifies IL 23 R as an ...We found a highly significant association between Crohn's disease and the IL 23 R gene on chromosome 1 p 31, which encodes a subunit of the receptor for the ...

 

 

Enovin, a member of the glial cell-line-derived neurotrophic ...chromosome 1, region p31.3-p32. In vitro, enovin stimulates neurite outgrowth and

content.febsjournal.org/cgi/reprint/266/3/892.pdf

 

 

From above post

 

http://www.burnham.org/print.asp?contentID=196

 

EphB2/syndecan-2 signaling in dendritic spine development

Dendritic spines are small protrusions on the surface of dendrites that receive the vast majority of excitatory synapses.

 

and

 

In a subsequent study, we demonstrated that syndecan-2 is phosphorylated on two tyrosine residues by EphB2, a receptor tyrosine kinase that is also concentrated in dendritic spines. Syndecan-2 and EphB2 associate to form a complex in neurons and in the brain. Phosphorylation by EphB2 is necessary for syndecan-2 to associate with EphB2 and to induce dendritic spine formation in cultured neurons.

 

 

http://genome-www.stanford.edu/cgi-bin/gen...p.pl?gene=EPHB2

 

Entrez Gene cytogenetic band: 1p36.1-p35 Ensembl cytogenetic band: 1p36.12 HGNC cytogenetic band: 1p36.1-p35

 

MTHFR is also found in this area

[kim]

http://www.jneurosci.org/cgi/content/full/20/21/7932

 

Regulation of AMPA Receptor GluR1 Subunit Surface Expression by a 4.1N-Linked Actin Cytoskeletal Association (bolding mine)

 

 

the most likely explanation for the deficiency of protein 4.1 in the family. We assigned the gene for erythrocyte protein 4.1 to the short arm (p) of chromosome 1, within a region from band 32 to the terminus (1p32----1pter). Other cases of hereditary elliptocytosis of unknown cause have been mapped to the same region of chromosome 1 by linkage to the Rh locus.

 

and

 

Moreover, disruption of actin filaments in cultured cortical neurons dramatically reduced the level of surface AMPA receptors.