Innovating Works

SAF2011-26983

Financiado
SURGENDIS: APELLIDOS, GENES Y ENFERMEDAD. ESTUDIO GENOMICO DE RELACIONES DE PARE...
SURGENDIS: APELLIDOS, GENES Y ENFERMEDAD. ESTUDIO GENOMICO DE RELACIONES DE PARENTESCO LEJANAS EN POBLACIONES HUMANAS E IMPLICACIONES BIOMEDICAS THE (I) BASIS OF HUMAN GENETIC COMPLEX DISEASE, (II) THE KNOWLEDGE OF THE EVOLUTIONARY HISTORY OF HUMAN POPULATIONS, AND (III) VARIOUS BIOMEDICAL APPLICATIONS, SUCH AS FORENSIC GENETICS, UNDERLIE IN THE DISTRIBUTION OF GENETIC VAR... THE (I) BASIS OF HUMAN GENETIC COMPLEX DISEASE, (II) THE KNOWLEDGE OF THE EVOLUTIONARY HISTORY OF HUMAN POPULATIONS, AND (III) VARIOUS BIOMEDICAL APPLICATIONS, SUCH AS FORENSIC GENETICS, UNDERLIE IN THE DISTRIBUTION OF GENETIC VARIABILITY IN POPULATIONS. ALL HUMAN BEINGS ARE RELATED TO EACH OTHER TO A MORE OR LESS DEGREE OF ANCESTRY; THUS FOR INSTANCE, THE WELL-KNOWN RETROSPECTIVE MODEL OF THE COALESCENT THEORY INDICATES THAT IT IS POSSIBLE TO TRACE ALL ALLELES OF A GENE SHARED BY ALL MEMBERS OF THE POPULATION TO A SINGLE ANCESTRAL COPY (THE MOST RECENT COMMON ANCESTOR; MRCA; SOMETIMES ALSO TERMED THE CO-ANCESTOR TO EMPHASIZE THE COALESCENT RELATIONSHIP). THEORETICAL MODELS HAVE ALSO DEMONSTRATED THAT THE STUDY OF THE GENOME TO A HIGH LEVEL OF RESOLUTION COULD REVEAL DISTANT RELATIONSHIPS WITH HIGH PRECISION ENABLING TO PREDICT THE PROBABILITY OF A GIVEN DISTANT GENEALOGICAL RELATIONSHIPS. WE HERE PROPOSE AN EMPIRICAL NOVEL APPROACH TO THE STUDY OF THE HUMAN CO-ANCESTRY THAT CONSISTS OF THE ANALYSIS OF POPULATION RELATIONSHIPS THROUGH THE INVESTIGATION OF IDENTITY BY DESCENT (IBD) ASSESSED IN DIFFERENT PREDEFINE (THEORETICAL) POPULATION STRATA. THEORY ALSO INDICATES THAT SPECIFIC GENEALOGICAL RELATIONSHIPS SHARING EQUAL IBD’S CAN BE UNRAVELED WHEN USING HIGHLY LINKED LOCI. THUS, DISTANT RELATIONSHIPS WILL BE ASSESSED IN (I) DONORS SHARING THE FIRST SURNAME (SINCE IT HAS BEEN DEMONSTRATED TO BE HIGHLY CORRELATED WITH THE Y-CHROMOSOME), (II) INDIVIDUALS SUFFERING A COMPLEX DISEASE (ASSUMING A COHORT OF PATIENTS TO BE INDIVIDUALS MORE CLOSELY RELATED EACH OTHER THAN EXPECTED BY CHANCE), AND (III) BY GEOGRAPHY (ASSUMING THAT GEOGRAPHICAL DISTANT PLAYS AN IMPORTANT ROLE IN SHARING CO-ANCESTRY). UNIPARENTAL MARKERS (Y-CHROMOSOME AND MITOCHONDRIAL DNA) AND GENOME-WIDE ANALYSIS (GWAS; ~650.000 SINGLE NUCLEOTIDE POLYMORPHISMS OR SNPS) WOULD IN THEORY ALLOW TO REVEAL DISTANT RELATIONSHIPS THAT COULD EXPLAIN PART OF THE VARIATION RESPONSIBLE FOR THE PREDISPOSITION TO COMPLEX DISEASES AND WOULD ALLOW TO MAKE INFERENCES ON THE MOST LIKELY GEOGRAPHICAL ORIGIN OF A GIVEN BIOLOGICAL SOURCE IN EVIDENTIARY SAMPLES (INFORMATION THAT IS OF PRIMARY INTEREST IN FORENSIC CASEWORK). GENOTYPING WILL BE CARRIED OUT IN A SAMPLE OF 450 HEALTHY INDIVIDUALS OF KNOWN GEOGRAPHICAL ORIGIN THAT SHARE THE FIRST SURNAME. GENOME-WIDE DATA FROM COHORTS OF PATIENTS AND CONTROLS (FOR WHICH GEOGRAPHICAL ORIGIN IS ALSO KNOWN) ARE ALREADY AVAILABLE BY THE IP (AS PART OF OTHER COLLABORATIVE STUDIES) AND WILL ALLOW TESTING THE HYPOTHESIS OF THE PROJECT IN CONJUNCTION WITH THE NEW GENOTYPES OBTAINED FOR THE INDIVIDUALS ASSESSED BY SURNAMES. THESE COHORTS INVOLVE >1,000 MENINGOCOCCAL PATIENTS (SPANISH AND UK COHORTS) WITH THE RESPECTIVE >1,500 HEALTHY SPANISH CONTROLS, AND >1,000 COLON CANCER SPANISH PATIENTS WITH THE RESPECTIVE >1,300 CONTROLS. MASSIVE DATA FROM THE WELCOME TRUST (EUROPEAN COHORTS) IS ALSO AVAILABLE BY THE IP AFTER OBTAINING THE FAVORABLE PERMISSION FROM THE INSTITUTION. ONE OF THE MAIN GOALS OF THE PRESENT PROJECT IS TO DIG INTO THE DIFFERENT LEVELS OF DISTANT RELATIONSHIPS IN A HUMAN POPULATION THAT WOULD UNDERLAY ON THE BASES OF THE COMPLEX DISEASE AND WILL ALSO ALLOW THE INTRODUCTION OF A NEW GENOMIC-BASED PREDICTIVE MODEL. THE SECOND GOAL IS TO EXPLORE TO WHAT EXTENT THE INFORMATION WRITTEN ON THE GENOME COULD SERVE THE INTERESTS OF FORENSIC GENETICS, WHEN CORRELATING GENOME INFORMATION WITH SURNAMES AND/OR THE MOST LIKELY GEOGRAPHIC ADSCRIPTION. WAS\ENFERMEDAD COMPLEJA\IBD\CROMOSOMA Y\MTDNA\MARCADORES UNIPARENTALES ver más
01/01/2011
USC
121K€
Perfil tecnológico estimado

Línea de financiación: concedida

El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2011-01-01
Presupuesto El presupuesto total del proyecto asciende a 121K€
Líder del proyecto
UNIVERSIDAD DE SANTIAGO DE COMPOSTELA No se ha especificado una descripción o un objeto social para esta compañía.
Total investigadores 234