Functional annotation of genomic signatures using array CGH and NGS analysis of phenotypic variants with Mendelian inheritance.  Page description

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Details of project

 
Identifier
103983
Type K
Principal investigator Melegh, Béla
Title in Hungarian Genomikus elemek functionális annotálása Mendeli öröklésmenetű fenotípus variánsok array CGH és NGS analízisével.
Title in English Functional annotation of genomic signatures using array CGH and NGS analysis of phenotypic variants with Mendelian inheritance.
Keywords in Hungarian Annotálás, DNS, array CHG, új generációs szekvenálás, fenotípus
Keywords in English Annotation, DNA, array CGH, Nex gen sequencing, rare diseases, phenotypic variants
Discipline
Genetic epidemiology (Council of Medical and Biological Sciences)50 %
Biological basis of diseases related to the above (Council of Medical and Biological Sciences)30 %
Public health, health services, environmental and occupational medicine, epidemiology, medical ethics (Council of Medical and Biological Sciences)20 %
Ortelius classification: Medicine
Panel Genetics, Genomics, Bioinformatics and Systems Biology
Department or equivalent Insitute of Medical Genetics (University of Pécs)
Participants Berenténé Bene, Judit Ágnes
Czakó, Márta
Hadzsiev, Kinga
Halmainé dr. Komlósi, Katalin
Járomi, Luca
Kisfali, Péter
Komoly, Sámuel
Magyari, Lili
Sipeky, Csilla
Starting date 2012-10-01
Closing date 2017-07-31
Funding (in million HUF) 27.948
FTE (full time equivalent) 5.25
state running project





 

Final report

 
Results in Hungarian
A pályázat során el sikerült érni azokat a célokat, melyek a terveztben szerepeltek, sőt, sikerült több természetes kiterjesztést is sikeresen kivitelezni. Több új gén ill. variáns került annotálásra, több új beteg fenotípus került felismerésre, több új átrendeződést sikerült karakterizálni. Számos funkcionális sajátosságokkal bíró genetikai variáns előfordulási gyakoriságában populációgenetikai különbségeket találtuk. A monogénes ill. a genomikai betegségek terén új fenotípusokat ismertünk meg, melyek tudományos értelemben funkcionális annotálásnak felelnek meg; a klinikum, azaz a beteg vonatkozásában, ez diagnózist jelentett. A terveknek megfelelően sikerrel alkalmaztuk ill. gyarapítottuk biobank készleteinket, számos új nemzetközi kollaborációba sikerült bekapcsolódni közvetlenül vagy indirekten a jelen pályázathoz csatlakozóan. A pályázat során 29 eredeti közleményünk jelet meg, 8 további közlés alatt áll; az eredményeket több nemzetközi konferencián sikerült bemutatnunk; a témavezető két nemzetközi konferencia meghívást is kapott plenáris előadás tartásra. Összesen 5 jelölt szerzett PhD minősítést a pályázat eredményeinek köszönhetően, 2 további hallgató anyaga már bírálók elött van.
Results in English
In the project all goals were succesfully implemented, in some cases certain natural extension also were achieved. We annotated new genes and genetic variants, we describen new phenotypic variants, including new genomic rearrangments. In a spectrum of functional genetic variants we found population genetic differences. In the genetic and genomic disease groups we desribed new pehotypes, that correspond to novel gene annotations in scientific context, while in the clinics they meant diagnosis for the patients, and patient's families. According to the origainl plans we succesully utilized and gained our biobank collections; we could establish new domestic and international scientific collaborations. We got 29 International, peer reviewed research papers, 8 works are under publication; we also had numerous conference presentations, the group leader had 3 invitations to present plenary lectures in International meetings. A total of 5 candidates got PhD degree, 2 theses are submitted.
Full text https://www.otka-palyazat.hu/download.php?type=zarobeszamolo&projektid=103983
Decision
Yes





 

List of publications

 
Szalai R, Ganczer A, Magyari L, Matyas P, Bene J, Melegh B.: Interethnic differences of cytochrome P450 gene polymorphisms may influence outcome of taxane therapy in Roma and Hungarian populations., Drug Metab Pharmacokinet., 2015
Kövesdi E, Bene J, Nagy N, Horváth Á, Melegh B, Hadzsiev K.: Importance of gross deletions in the diagnosis of tuberous sclerosis complex: the first Hungarian cases, Orv Hetil., 2017
Tripolszki K, Farkas K, Sulák A, Szolnoky G, Duga B, Melegh B, Knox RG, Parker VER, Semple RK, Kemény L, Széll M, Nagy N.: Atypical neurofibromatosis type 1 with unilateral limb hypertrophy mimicking overgrowth syndrome., Clin Exp Dermatol., 2017
Fekete A, Hadzsiev K, Bene J, Nászai A, Mátyás P, Till Á, Melegh B: A8344G mitochondrial DNA mutation observed in two generations, Orv Hetil, 2017
Fischer S, Kövesdi E, Magyari L, Csöngei V, Hadzsiev K, Melegh B, Hegyi P, Sarlós P: IL23R single nucleotide polymorphisms could be either beneficial or harmful in ulcerative colitis., World J Gastroenterol., 2017
Sumegi K, Duga B, Melegh BI, Banfai Z, Kovesdi E, Maasz A, Melegh B: Marked Differences of Haplotype Tagging SNP Distribution, Linkage, and Haplotype Profile of APOA5 Gene in Roma Population Samples., Pathol Oncol Res., 2017
Szalai R, Hadzsiev K, Melegh B: Cytochrome P450 Drug Metabolizing Enzymes in Roma Population Samples: Systematic Review of the Literature., Curr Med Chem., 2016
Seidel K, Siswanto S, Fredrich M, Bouzrou M, den Dunnen WFA, Özerden I, Korf HW, Melegh B, de Vries JJ, Brunt ER, Auburger G, Rüb U.: On the distribution of intranuclear and cytoplasmic aggregates in the brainstem of patients with spinocerebellar ataxia type 2 and 3., Brain Pathol., 2017
Komlosi K, Hadzsiev K, Garbes L, Martínez Carrera LA, Pál E, Sigurðsson JH, Magnusson O, Melegh B, Wirth B.: Exome sequencing identifies Laing distal myopathy MYH7 mutation in a Roma family previously diagnosed with distal neuronopathy, Neuromuscular Disord, 2013
Lazaridis I, Patterson N, .......Melegh B,.......Reich D, Krause J.: Ancient human genomes suggest three ancestral populations for present-day Europeans., Nature, 2014
Szalai R, Matyas P, Varszegi D, Melegh M, Magyari L, Jaromi L, Sumegi K, Duga B, Kovesdi E, Hadzsiev K, Melegh B.: Admixture of beneficial and unfavourable variants of GLCCI1 and FCER2 in Roma samples can implicate different clinical response to corticosteroids., Mol Biol Rep., 2014
Ripke S, Neale BM,.....Melegh B,........Sullivan PF, O'Donovan MC: Biological insights from 108 schizophrenia-associated genetic loci., Nature, 2014
Sipeky C, Matyas P, Melegh M, Janicsek I, Szalai R, Szabo I, Varnai R, Tarlos G, Ganczer A, Melegh B.: Lower carrier rate of GJB2 W24X ancestral Indian mutation in Roma samples from Hungary: implication for public health intervention., Mol Biol Rep., 2014
Duga B, Czako M, Komlosi K, Hadzsiev K, Torok K, Sumegi K, Kisfali P, Kosztolanyi G, Melegh B.: Deletion of 4q28.3-31.23 in the background of multiple malformations with pulmonary hypertension., Mol Cytogenet., 2014
Pár A, Pár G, Tornai I, Szalay F, Várszegi D, Fráter E, Papp M, Lengyel G, Fehér J, Varga M, Gervain J, Schuller J, Nemes Z, Péterfi Z, Tusnádi A, Hunyady B, Haragh A, Szinku Z, Vincze A, Szereday L, Kisfali P, Melegh B.: IL28B and IL10R -1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European, BMC Res Notes., 2014
Magyari L, Varszegi D, Sarlos P, Jaromi L, Melegh BI, Duga B, Kisfali P, Kovesdi E, Matyas P, Szabo A, Szalai R, Melegh B.: Marked differences of haplotype tagging SNP distribution, linkage, and haplotype profile of IL23 receptor gene in Roma and Hungarian population samples., Cytokine, 2014
Varszegi D, Duga B, Melegh BI, Sumegi K, Kisfali P, Maasz A, Melegh B.: Hodgkin disease therapy induced second malignancy susceptibility 6q21 functional variants in roma and hungarian population samples., Pathol Oncol Res., 2014
Nagy A, Sipeky C, Szalai R, Melegh BI, Matyas P, Ganczer A, Toth K, Melegh B.: Marked differences in frequencies of statin therapy relevant SLCO1B1 variants and haplotypes between Roma and Hungarian populations., BMC Genet., 2015
Sipeky C, Weber A, Melegh BI, Matyas P, Janicsek I, Szalai R, Szabo I, Varnai R, Tarlos G, Ganczer A, Melegh B.: Interethnic variability of CYP4F2 (V433M) in admixed population of Roma and Hungarians., Environ Toxicol Pharmacol., 2015
Szabo A, Czako M, Hadzsiev K, Duga B, Komlosi K, Melegh B.: Partial tetrasomy of the proximal long arm of chromosome 15 in two patients: the significance of the gene dosage in terms of phenotype., Mol Cytogenet., 2015
Nagy A, Szalai R, Magyari L, Bene J, Toth K, Melegh B.: Extreme differences in SLCO1B3 functional polymorphisms in Roma and Hungarian populations., Environ Toxicol Pharmacol, 2015
Weber A, Szalai R, Sipeky C, Magyari L, Melegh M, Jaromi L, Matyas P, Duga B, Kovesdi E, Hadzsiev K, Melegh B.: Increased prevalence of functional minor allele variants of drug metabolizing CYP2B6 and CYP2D6 genes in Roma population samples., Pharmacol Rep., 2015
Komlósi K, Duga B, Hadzsiev K, Czakó M, Kosztolányi G, Fogarasi A, Melegh B.: Phenotypic variability in a Hungarian patient with the 4q21 microdeletion syndrome., Mol Cytogenet., 2015
Sumegi K, Jaromi L, Magyari L, Kovesdi E, Duga B, Szalai R, Maasz A, Matyas P, Janicsek I, Melegh B.: Functional variants of lipid level modifier MLXIPL, GCKR, GALNT2, CILP2, ANGPTL3 and TRIB1 genes in healthy Roma and Hungarian populations., Pathol Oncol Res., 2015
Szalai R, Ganczer A, Magyari L, Matyas P, Bene J, Melegh B.: Interethnic differences of cytochrome P450 gene polymorphisms may influence outcome of taxane therapy in Roma and Hungarian populations., Drug Metab Pharmacokinet., 2015
Szalai R, Hadzsiev K, Melegh B.: Cytochrome P450 Drug Metabolizing Enzymes in Roma Population Samples Systematic Review of the Literature., Curr Med Chem, 2016
Mehta D, Tropf FC, Gratten J,...Melegh B,....Weinberger DR, Weiser M, Wu JQ: Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women., JAMA Psychiatry., 2016
Hadzsiev K, Komlosi K, Czako M, Duga B, Szalai R, Szabo A, Postyeni E, Szabo T, Kosztolanyi G, Melegh B.: Kleefstra syndrome in Hungarian patients: additional symptoms besides the classic phenotype., Mol Cytogenet., 2016
Franke B, Stein JL, Ripke S,...Melegh B,...Neale BM, Medland SE, Sullivan PF: Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept., Nat Neurosci., 2016
Sekar A, Bialas AR, de Rivera H,...Melegh B,...Carroll MC, Stevens B, McCarroll SA: Schizophrenia risk from complex variation of complement component 4., Nature, 2016




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