ipek ilgın gönenç december, 2016 universitat autònoma de...
TRANSCRIPT
IpekIlgınGönençDecember,2016UniversitatAutònomadeBarcelona
GeneCcVariaCons,phenotypicandgenotypicdifferencesamongindividualsorinapopulaCon.Polymorphisms,variaConsinsomepartsoftheDNAamongindividuals(differentalleles).
IntroducCon,somedefiniCons
SNPs(singlenucleoCdepolymorphism):nucleoCdesubsCtuCons.- MostSNpsarefoundinnoncodingregions.- Ocurrencyfrequencybetween1/1000and1/100.
VNTRs(variablenumberoftandemrepeatpolymorphism):tandemlyrepeatedrunsofasimplesequence.CNVs(copynumbervariaCon)inserCon-deleConvariants....
IntroducCon,somedefiniCons
TheInternaConalHapMapProject(2002-2005-2007-2009),- theaimwastodevelopeahaplotypemapofhumangenometodescribe
humangeneCcvariaCon.- thefocuswasoncommonSNPswitheachalleleoccuringatleastin1%of
populaCon.
Haplotypesarepa`ernsofDNApolymorphismsalongchromosomes.Ahaplogroup,isagroupofsimilarhaplotypessharingacommonancestor.
IntroducCon,theHapMapproject
TheInternaConalHapMapProjectNCBIre(ringHapMapResourceJune16,2016A recent computer security audit has revealed security flaws in the legacyHapMap site that require NCBI to take it down immediately. We regret theinconvenience,butwearerequiredtodothis.Thatsaid,NCBIwasplanningtodecommission this site in the near future anyway (although not quite sosuddenly), as the 1,000 genomes (1KG) project has established itself as aresearchstandardforpopulaCongeneCcsandgenomics.NCBIhasobservedadeclineinusageoftheHapMapdatasetandwebsitewithitsavailableresourcesoverthepastfiveyearsandithascometotheendofitsusefullife.
IntroducCon,however...
HumanY-chromosomeDNAhaplogroupsMitochondrialDNAhaplogroups,
IntroducCon,Examplestohaplogroups
Examplesofvariatonsamonghumans
HLA(HumanleukocyteanCgen):• AgenecomplexinChr6thatcodesforMajorHistocompaCbilityComplex
(MHC)proteinsthatareresponsibleproteinsonimmunesysteminhumans.• HLAgenearethehighlypolymorphic(adapCveimmunesystem)• Importantfortransplantprocedures,HLAdifferencescausetherejecConof
theimplantedorgan.
doi:10.1371/journal.pone.0014643
TheDuffybloodtypes
Examplesofvariatonsamonghumans
- TheDuffyglycoproteinisareceptorforchemicalsthataresecretedbybloodcellsduringinflammaCon.
- ItalsohappenstobeareceptorforPlasmodiumvivax,aparasitethatinvadesredbloodcells(RBCs)andcausesmalariaviainvasionofRBCs.
- Therearefouralleles,combiningtoproduce4phenotypes.
• RBCsthatlacktheDuffyanCgensarerelaCvelyresistanttoinvasionbyP.vivax.
TheDuffybloodtypes
Examplesofvariatonsamonghumans
- TheDuffyglycoproteinisareceptorforchemicalsthataresecretedbybloodcellsduringinflammaCon.
- ItalsohappenstobeareceptorforPlasmodiumvivax,aparasitethatinvadesredbloodcells(RBCs)andcausesmalariaviainvasionofRBCs.
- Therearefouralleles,combiningtoproduce4phenotypes.
• RBCsthatlacktheDuffyanCgensarerelaCvelyresistanttoinvasionbyP.vivax. • ThecommonDuffyallelesshowstrikingpa`ernsofgeographic
differenCaCon.• TheDuffynullphenotype,Fy(a-b-),isveryrareinCaucasiansbutisfoundin
68%ofBlackpeople.
TheDuffybloodtypes
Examplesofvariatonsamonghumans
SimonI.Hayet.al(2011)
TheDuffybloodtypes
Examplesofvariatonsamonghumans
SimonI.Hayet.al(2011)
Thalassaemia
Examplesofvariatonsamonghumans
- ThalassaemiaisabloodrelatedgeneCcdisorderwhichinvolveserrorsingenesresponsibleforproducConofhaemoglobin,hencetheabsenceofprotein.
- Ahaemoglobinmoleculehassubunitscommonlyreferredasalphaandbeta.- Bothsubunitsarenecessarytobindoxygen.Differentgenesareresponsibleforthe
producConofsubunits.AlackofaparCcularsubunitdeterminesthetypeofthalassaemia.(eg.alackofalphasubunitsresultsinalpha-thalassemiaorbeta-thalassemia)
- Thebeta-thalassemiaisparCcularlywidespreadamongtheMediterraneanpeople(alsothenamecomesfromthesea).ThehighestcarrierfrequencyisreportedinCyprus,Sardinia,andSoutheastAsia.
Thalassaemia
Examplesofvariatonsamonghumans
- ThalassaemiaisabloodrelatedgeneCcdisorderwhichinvolveserrorsingenesresponsibleforproducConofhaemoglobin,hencetheabsenceofprotein.
- Ahaemoglobinmoleculehassubunitscommonlyreferredasalphaandbeta.- Bothsubunitsarenecessarytobindoxygen.Differentgenesareresponsibleforthe
producConofsubunits.AlackofaparCcularsubunitdeterminesthetypeofthalassaemia.(eg.alackofalphasubunitsresultsinalpha-thalassemiaorbeta-thalassemia)
- Thebeta-thalassemiaisparCcularlywidespreadamongtheMediterraneanpeople(alsothenamecomesfromthesea).ThehighestcarrierfrequencyisreportedinCyprus,Sardinia,andSoutheastAsia.
Islands??
TheAshkenaziJews
ExamplesofvariaCon,anidealpopulaCon
• TheyareagoodpopulaConforresearchbecauseoftheirendogamy,yettheyaresizeable(bigpopulaConinsize)
• Hence,isawellstudiedethnicgroupintermsofgeneCcdisorders.• InpopulaConbo`leneckdeleteriousallelesbecomemoreprevalentbychance.
G.Rosneret.al(2009)
TheConceptofRace
• RaceistheclassificaConofhumansintogroupsbasedonphysicaltraits,ancestry,geneCcsorsocialrelaCons,ortherelaConsbetweenthem.
• Verycontraversial!• Canbebeneficialforclinicaluses(sickle-celldiseasebeing
morecommoninAfricanandMediterraneanpopulaConsthaninothers.)
• However,itwouldbefarpreferabletotestdirectlytheindividuals.
Thankyouforyoura`enCon!
References• BuhlerS,Sanchez-MazasA(2011)HLADNASequenceVariaConamongHuman
PopulaCons:MolecularSignaturesofDemographicandSelecCveEvents.PLOSONE6(2):e14643.doi:10.1371/journal.pone.0014643
• SimonI.Hayet.al(2011)TheglobaldistribuConoftheDuffybloodgroup.NatureCommunica:ons2,p:266.doi:10.1038/ncomms1265
• G.Rosneret.al(2009)GeneCcTesCnginIsrael:AnOverview.AnnualReviewofGenomicsandHumanGene:cs10(1)pp:175-192doi:10.1146/annurev.genom.030308.111406
• LynnBJorde&StephenPWooding(2004)GeneCcvariaCon,classificaConand´race´.NatureGene:cs36(11)s28-33
• MichaelYudell,DorothyRoberts,RobDeSalle,SarahTishkoff.(5February2016)TakingraceoutofhumangeneCcsScienceandSociety351(6273)