Genetic polymorphisms

Cindy Zuluaga Ramírez

Medicine student

Molecular Biology

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INTRODUCTION

Variotion in regulatoryDNA is what we call

Polymorphism.

This is one of the ways in wich we can detect

Polymorphisms.

Cross-Species Strategy Might Be a Powerful Tool for Studying Human Disease

ScienceDaily (Feb. 4, 2011)

Cross –species strategy

Specifically, the researchersevaluated 19 genes from 15 distinctgenomic regions identified in ahuman GWAS designed to identifygenes that influence Alzheimer´sdisease pathology.

FINDINGS IN THE TECHNIQUE

In six out of these 15 genomicregions, a causal gene wassubsequently identified in the flydisease model on the basis ofinteractions with the neurotoxicity ofTau protein, a well-knownconstituent of AD pathology.

OBSERVATIONS

I think that this technique is a huge improvement forgenetic studies, since scientists are taking informationfrom some other species in wich we could find somegenetic similarities in some diseases and making newfinds of the genetic basis of the disorder and get somenew treatments .

Genes That Link Nephritis to Autoantibodiesand Innate Immunity

THE NEW ENGLAND JOURNAL OF MEDICINE (FEBRUARY 17,2011)

FINDINGS

• The annual incidence of membranousnephropathy is approximately 1 caseper 100,000 population.

• The results reported by Stanescu etal. confirm the findings of two recentstudies from Asia (Taiwan and Korea)that used a candidate gene approach.Both those studies examined onlySNPs in the PLA2R gene that resultedin amino acid changes, and asignificant association was found forone SNP.

• Although a relation between the HLAsystem and membranous nephropathyhas been recognized for some time, theknowledge of an association betweenthis disease and PLA2R is recent. In 2009,Beck and colleagues reportedautoantibodies with specificity for PLA2Rthat were present in 70% of theirpatients with idiopathic membranousnephropathy but not in controls orpatients with secondary membranousnephropathy. These results are nowconfirmed and extended in a letter byDebiec and Ronco in this issue of theJournal.

The SNP in the PLA2R gene with the strongest association does not alter the amino acid

sequence

the true association might not bewith rs4664308 but rather withrs3749117, which is anonsynonymous SNP reported to bein linkage disequilibrium withrs4664308. If so, the higher oddsratios in all three cohorts would haveoccurred at random.

The rs4664308 might be a marker fora rare variation in the proteinsequence, below the thresholdrequired to be considered a SNP. Thisputative variant would then confer avery high risk of disease for itscarriers.

Two possible theories

CONCLUSSION

In summary, this new genomewide association study highlights theinteraction between the HLA system and the receptor for sPLA2 andprovides substantial credence for a pathogenic role for the recentlydiscovered autoantibodies in membranous nephropathy. It may redirectresearch toward finding a remedy for this troublesome disease.

OBSERVATIONS

I think this new discovery will make easier thediagnosis of idiopathic membranousnephropathy making karyotype and searchingchanges among the alleles implicated in thisdisorder that encode HLA-DQA1 and the M-typephospholipase A2 receptor.

MEDICAL UTILITY

MEDICAL UTILITY

Early diagnosis

Easy identification of the patients in risk

Early and quick begining of treatment

For the development and the sustentation of genetic studies .

BIBLIOGRAPHY

• N Engl J Med 2011; 364:679-680; http://www.nejm.org/doi/full/10.1056/NEJMe1014144

• http://www.sciencedaily.com/releases/2011/02/110203124712.htm

• STRACHAN, Tom. Human molecular genetics , 2004. 3.ed. Garland science