Strictly Science: not all may understand.

"The genetic etiology of age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is beginning to be unraveled with the discovery of the associations with Y402H in complement factor H (CFH) on chromosome 1 and LOC387715 A69S on chromosome 10." Human Molecular Genetics, 2008, Vol. 17, No. 7- 971–977

Could anyone help me understand this sentence. Specially, what does "Y402H"  mean?  One research paper has title "CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration". What does this 'coding variant of gene' mean? Y402H doesnt look like a name of a gene as it seems to me like a part of gene CFH. Does it represent certain AA sequence? I am lost.

Also, what does A69S mean? LOC387715 is a gene name ( OMIM#611313). But it does not include A69S part in OMIM.

Any help will be appreciated.

I have not reviewed the article , but from your writing here,  It looks like SNP or some other polymorphism

In general, when you have a capital letter followed by a number and another capital letter, its usually the site of mutation. So, in proteomics, Y402H and A69S stands for the mutation from of Y(tyrosine)402 to H(histidine) and A(alanine) 69 to S(serine).

However, in most of the genetic studies related with association studies, they use the microsatellite markers( its the portion of gene which is conserved among the species and used for DNA mapping) on a specific chromosome to calculate LOD score which specifies whether there is a link of particular portion of gene with the diseased phenotype. Having said that, Y402H and A69S could very  well be among couple of microsatellite markers they used in this study.

About coding varient of gene, its just the splice variant. I suppose you are familiar with gene trascription, translation process. After gene trasncription, the m-RNA processing occurs, which actually leads to various splice varinats and is the reason of various isoforms of same protien and also non-functional or hyperfunctional protiens, causing loss-of-function, or gain-of-function features.

I hope this helps, or am I making your situation more complex. Honestly, I hate genetics paper, and I don't think I would have time to read the paper you sited above.

Good luck with the paper!

Cannabis

here is the link to the paper for those interested. Enjoy!

http://hmg.oxfordjournals.org/cgi/content/full/17/7/971

I just did a quick googleing and it turns out the issue of mutations due to polymorphism. Below is the absract of the paper.

Complement Factor H Polymorphism in Age-Related Macular Degeneration

Robert J. Klein,¹ Caroline Zeiss,^2* Emily Y. Chew,^3* Jen-Yue Tsai,^4* Richard S. Sackler,¹ Chad Haynes,¹ Alice K. Henning,⁵ John Paul SanGiovanni,³ Shrikant M. Mane,⁶ Susan T. Mayne,⁷ Michael B. Bracken,⁷ Frederick L. Ferris,³ Jurg Ott,¹ Colin Barnstable,² Josephine Hoh⁷

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10^-7). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies.

¹ Laboratory of Statistical Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
² Department of Ophthalmology and Visual Science, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USA.
³ National Eye Institute, Building 10, CRC, 10 Center Drive, Bethesda, MD 20892-1204, USA.
⁴ Biological Imaging Core, National Eye Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA.
⁵ The EMMES Corporation, 401 North Washington Street, Suite 700, Rockville MD 20850, USA.
⁶ W. M. Keck Facility, Yale University, 300 George Street, Suite 201, New Haven, CT 06511, USA.
⁷ Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, New Haven, CT 06520, USA.

^* These authors contributed equally to this work.

To whom correspondence should be addressed. E-mail: josephine.hoh@yale.edu

Thank you Shivanagar and Cannabis. That helped a lot.