GENETICS - .GLOBAL...The 100,000 Genomes Project •The 100,000 Genomes Project is a research project, a clinical service and an NHS transformation project in one •100,000 whole

GENETICSThescienceofinheriteddisease

The100,000GenomesProjectWhat’sagenome?

HumanGenomeProjectFirstdraftsequence2000

• Theythoughtthey’dfindaminimumof100,000genes

• Theyfound20,000• That’sthesamenumberasastarfish

HowmuchofyourDNAisgenes?

•80%

•50%

•20%

• RestoftheDNAusedtobe‘junk’,wasn’tthoughttobeimportant.

• Nowknowit’simportantforregulation,switchinggenesonandoffattherighttime.

• Stillmuchmoretolearnaboutwhatitalldoes.

Genes:lessthan5%ofDNA

Genomics

Thescienceof

•all theDNAinthegenome•Andhowit’ssequenced,analysedandinterpreted

Howdifferentareourgenomes?•Moredifferencebetweenindividualsthanbetweendifferentraces

•Weare99.8%identical•But0.2%isstill3milliondifferences.Itswhatmakesyouyou

Thefirsthumangenomesequence

• 26th June 2000 - Cost $3.2 billion and took 13 years

Costofsequencing

Today it takes 24 hours costs less than $1000

The100,000GenomesProject

1.TobringbenefittoNHS

patients

2.Tocreateanethicalandtransparentprogrammebasedonconsent

3.Toenablenewscientificdiscoveryand

medicalinsights

4.Tokickstartthe

developmentofaUKgenomics

industry

The100,000GenomesProject

• The100,000GenomesProjectisaresearchproject,aclinicalserviceandanNHStransformationprojectinone

• 100,000wholegenomesfrom70,000patientsandtheirfamilieswithrarediseaseorcancer,completionby2018

• Basedonconsent• Recruitmentthrough13NHSGenomicMedicineCentres

………inanutshell

The100,000GenomesProject

• Sequencedatalinkedtohealthdatatodiagnose• Sequencedata,healthdataandlifelongmedicalrecorddataputintodatasetavailableforresearchincludingaccessbydrugcompanies

• NHSwillbefirsthealthsystemintheworldtoembedgenomicmedicineinmainstreamhealthcare

• Atthecuttingedgeofscienceandvery,veryhard.

………inanutshell

The100,000GenomesProject

Thebeginningofsomethingamazing

PersonalisedMedicine

1. Prediction andprevention ofdisease

2. Moreprecise diagnosis3. Targetedandpersonalised

interventions4. Amoreparticipatory rolefor

patients

New era of personalised medicine

THE 4 Ps:

Thefuture- startswithbeauty

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Prediction&Prevention

• Ofthe120,000peopleintheUKwithFHonly15%–lessthan1in5,knowtheyhavethecondition

• Atleast28,000childrenintheUKhaveFH butonly600oftheseareknown

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FamilialHypercholesterolaemia (FH)

16June2017

Image courtesy of Health Education England

Fivebabies:allthesamesymptoms

KCNJ11 p.V59MPermanentdiabetesanddevelopmental

delay

FOXP3 c.227delTIPEXsyndrome

EIF2AK3 p.E371*WolcottRallison

Syndrome

STAT3p.T716MMulti-organautoimmune

disease

GATA6 c.1448-1455delSyndromic

pancreaticagenesis

BoneMarrowTransplant

LiverTransplant

Sulphonylureatherapy

Insulinandexocrine

supplements

?STAT3inhibitor

MorePreciseDiagnosisTherightdiagnosisfirsttime

Therighttreatmentfirsttime

• 8000NHSbedsadayoccupiedbypeoplewhohavehadadversedrugevents(6.5%oftotalbeds)

• 70%ofthewaythatdrugsaremetabolisedisthroughthecytochromep450pathway

• Manydrugsaffectedbygeneticvariantse.g.codeine,abacavir,warfarin

• Rightantibioticsfirsttime

Pharmacogenomics

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Personalised&targeted

• Highlytargeted• PanelsorWGS?Juryisout.• Expensivedrugsonlyforthoseforwhomitwillwork

• Ifresistancedevelops,re-sequence

• Abaselineifcancerreturns• Providesdatasetforfutureclinicaltrials

Cancercare

AParticipatoryroleforpatients

• Wellnessratherthanillness• Approachwithcaution

Ethics

• Wholegenomesequencingatbirth• Whataboutbeforebirth?• Whatdowewanttoknow?• WhatdowewantNOTtoknow?• Howsuredowehavetobe?• Over-diagnosis?

Wherewillthistechnologytakeus?

Whatthefutureisnot

•Genomicsingeneticsdepartments

Thefuture

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