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GOOD AFTERNOON, MY NAME IS
DR. DANIEL SHERTOW, WELCOME TO
TODAY'S LIVE CLINICAL CENTER
GRAND ROUNDS PRESENTATION.
THE HOPKINS CLOUD CME CODE FOR
TODAY'S GRAND ROUNDS IS 36728.
PLEASE TEXT THIS CODE TO THE
JOHNS HOPKINS CME PHONE NUMBER
ON THE SLIDE TO RECEIVE CME
CREDIT FOR THIS LECTURE.
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FORM FOR TODAY'S LECTURE IS
AVAILABLE AS WAY DOWNLOADABLE
PDFOT CLINICAL CENTER GRAND
ROUNDS WEBSITE.
THIS FORM IS USED TO PROVIDE US
WITH IMPORTANT FEEDBACK ABOUT
THIS PRESENT HAITIAN AND ALLOWS
YOU TO SUBMIT ANY SUGGESTIONS
FOR FUTURE GRAND ROUNDS TOPICS.
QUESTIONS FOR THE SPEAKER CAN BE
SUBMITTED AT ANY TIME DURING THE
LECTURE BY SCROLLING DOWN AND
CLICKING THE LIVE FEEDBACK
BUTTON LOCATED ON THE VIDEOCAST
WEBSITE.
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TIME PERMITS AT THE CONCLUSION
OF THE PRESENTATION.
OW SPEAKER TODAY IS DR. CHARLES
ROTIMI, SCIENTIFIC DIRECTOR AND
NIH DISTINGUISHED INVESTIGATOR
FOR THE IMPOSSIBLE TO BUILD
RAMURAL RESEARCH AND THE
NATIONAL HUMAN GENOME RESEARCH
INSTITUTE, HE'S ALSO THE
DIRECTOR FOR CENTER FOR RESEARCH
ON GENOMICS AND GLOBAL HEALTH.
DR. ROTIMI RECEIVED HIS
BACHELORS IN BIOCHEMISTRY FROM A
UNIVERSITY OF NIGERIA, HE
PURSUED A MASTERS FROM THE
UNIVERSITY OF MISSISSIPPI AND
EARNED A MASTERS PUBLIC HEALTH
AND Ph.D. IN EPIDEMIOLOGY FROM
THE UNIVERSITY OF ALABAMA AT
BIRMINGHAM.
AFTER COMPLETING HIS Ph.D.
DR. ROTIMI WORKED AS AN
ASSISTANT PROFESSOR BEFORE
BECOMING A ASSOCIATE PROFESSOR
FOR THE DEPARTMENT OF MEDICINE
AND EPIDEMIOLOGY AT LOYALA
UNIVERSITY MEDICAL CENTER IN
ILLINOIS.
FROM 1999-2008 DR. ROTIMI SERVED
AS DIRECTOR OF GENETIC
EPIDEMIOLOGY FOR THE NATIONAL
HUMAN GENOME CENTER AT HOWARD
UNIVERSITY COLLEGE OF MEDICINE.
HE BECAME A TENURED PROFESSOR
FOR THE DEPARTMENT OF COMMUNITY
AND FAMILY MEDICINE AT HOWARD IN
2003 AND THE DIRECTOR FOR THE
HUMAN, THE NATIONAL HUMAN GENOME
CENTER AT HOWARD IN 2004.
DR. ROTIMI CAME TO THE NIH IN
2008 TO FOUND THE CENTER FOR
RESEARCH AND GENOMICS AND GLOBAL
HEALTH WITH THE MISSION OF
ADVANCING RESEARCH INTO THE ROLE
OF CULTURE, LIFESTYLE AND
GENOMICS AND DISEASE ETIOLOGY,
HEALTH DISPARITIES AND VARIABLE
DRUG RESPONSE.
DR. ROTIMI'S RESEARCH FOCUSES ON
THE ETIOLOGY OF COMPLEX DISEASES
AND HEALTH DISPARITIES.
HIS TEAM STUDIES ETHNIC
DIFFERENCES IN THE DISTRIBUTION
OF GENETIC AND ENVIRONMENTAL
RISK FACTORS WITH PARTICULAR
EMPHASIS ON POPULATIONS OF
AFRICAN ANCESTRY.
DR. ROTIMI'S LAB DEVELOPS MODELS
AND CONDUCTS STUDIES THAT
EXPLORE THE PATTERNS AND
DETERMINANTS OF COMMON COMPLEX
DISEASES AND HUMAN POPULATION
ISSUES WITH THE PARTICULAR
EMPHASIS OF POPULATIONS WITH THE
AFRICAN DISP A ARA, HIS LAB
CONTRIBUTED TO THE GLOBAL
UNDERSTANDING OF HUMAN VARIATION
BY ACTIVELY PARTICIPATE NOTHING
THE ACTIVE GENOMES AND THE
AFRICAN GENOME PROJECT.
HE IS ON THE EXECUTIVE AND
SCIENTIFIC COMMITTEE FOR
INTERNATIONAL FEDERATION OF
HUMAN GENETIC STOATS AND ELECTED
TO THE HUGO COUNCIL.
HE IS THE FOUNDING AND PAST
PRESIDENT OF THE AFRICAN SOCIETY
OF HUMAN GENETICS.
DR. OTIMI LED THE ESTABLISHMENT
OF HUMANITARIAN INITTIA WITH
76 MILLION COMMITMENT FROM THE
NIH AND THE WELCOME TRUST.
H3 AFRICA CREATED A SUPPORT
NETWORK OF LABS THAT CONDUCTED
LEADING EDGE RESEARCH INTO THE
GENETIC AND ENVIRONMENTAL
DETERMINANTS OF DISEASE IN
AFRICANS.
HE IS ON THE EDITORIAL BOARD OF
PUBLIC HEALTH GENOMICS, GENOMIC
MEDICINE, CLENICAL GENETICS
JOURNAL OF APPLIED TRANSLATIONAL
GENOMICS AND THE CORNELL
PERSONALIZED MEDICINE
COLLABORATIVE BOARD.
AWARDED AN HONORARY
PROFESSORSHIP AT THE UNIVERSITY
OF CAPE TOWN SOUTH AFFRIC
ABECAME THE CHIEF OF
CARDIOVASCULAR AND METAGENOMIC
BRARCH OF 2014 AND HE STEPPED
DOWN IN 2021.
THE TIELTS OF HIS TALK TODAY IS
ANCESTRY, AND DISEASE AND THE
AGE OF PRECISION MEDICINE,
PLEASE JOIN ME IN WELCOMING
TODAY'S GRAND ROUNDS SPEAKER
DR. ROTIMI.
>> THANKS VERY MUCH DOCTOR FOR
THAT WONDERFUL INTRODUCTION AND
I'M GOING TO DO HARD WORK TO
MAKE SURE I KEEP UP WITH THAT
INTRODUCTION.
I'M GOING TO SHARE MY SLIDE NOW
LET'S SEE HERE.
SO DO YOU SEE AND HEAR ME OKAY.
>> YES.
>> FANTASTIC.
YES, I'M REALLY HONORED TO
CONDUCT THIS GRAND ROUND FOR THE
CLINICAL CENTER AND MY GOAL
TODAY IS TO SHARE WITH YOU SOME
OF THE WORK THAT YOU ALREADY
HEARD IN MY INTRODUCTION AT THE
CENTER FOR GENOMICS AND GLOBAL
HEALTH AND ALSO TO USE OTHER
PEOPLE'S WORK TO TALK TO YOU
ABOUT HOW I VIEW ANCESTRY AND
HOW, WHY ANCESTRY IS IMPORTANT
IN GENOMICS AND HOW WE DEPLOY
GENOMICS GLOBALLY TO MAKE SURE
THAT WE ARE TRYING TO GAIN THE
EQUITABLE DISTRIBUTION OF
PRECISION MEDICINE.
SO YOU ALREADY HEARD ABOUT THE
MISSION OF THE CENTER AND I WILL
NOT REPEAT THAT BUT IMPORTANTLY
IS THAT AT THIS CENTER BECAUSE
OF WHAT WE FOCUS ON, WE ACTUALLY
HAVE A MULTIETHNIC AND
INDIVIDUALS FROM ALL OVER THE
WORLD IN OUR LAB AND WE ARE
EXTREMELY PROUD OF THAT AND
SOMETIMES THEY CALL US THE
LITTLE UNITED NATIONS BECAUSE OF
THE COMBINATION OF PROFESSIONALS
FROM DIFFERENT PARTS OF THE
WORLD BUT AT THE CENTER WE'RE
REALLY INTERESTED IN GENETIC,
EPIGENETIC AND TRAITS AND WE DO
GENETIC IS IT THES TO UNDERSTAND
THE DISTRIBUTION OF VARIATIONS
AND HOW THEY IMPACT OUR HISTORY
AND HEALTH.
AND WE ALSO, YOU KNOW CONDUCT
RESEARCH AT WHAT I CALL THE
JUNCTION OF GENOMICS AND SOCIETY
TO UNDERSTAND THINGS LIKE
EQUITY, DISTRIBUTION OF HOW WE
DO BIOMEDICAL RESEARCH, AND
GENOMICS STUDIES SPECIFICALLY
AND SOMETIMES WE DEVELOP SPECIAL
[INDISCERNIBLE] OR IMPROVE
EXISTING 1S BECAUSE OF THE
POPULATIONS THAT WE STUDY SO
THAT'S BASICALLY THE WORK THAT
WE DO AT THE CENTER AND MOAOF
THED OF THE DATA YOU WILL SEE IN
MY PRESENTATION TODAY, ARE
PRODUCED IN THE CENTER AND ALSO
BORROWED FROM OTHER SCIENTISTS
AROUND THE WORLD.
SO THE FIRST POINT AGAIN, A
MAJOR PART OF THE TITLE OF MY
TALK IS THE CONCEPT OF ANCESTRY.
WHAT DOES IT REALLY MEAN WHEN WE
TALK ABOUT ANCESTRY, WHAT DO WE
MEAN?
IT SEEMS LIKE A PREVIOUS
STRAIGHT FORWARD CONCEPT BUT I
CAN SHOW YOU, IT'S REALLY NOT
THAT STRAIGHT FORWARD BECAUSE
THE MEANING AND THE WAY PEOPLE
USE IT VARIES BY CONTEXT AND I
WILL TRY TO TELL YOU HOW WE LOOK
AT IT IN TERMS OF GENOMICS AND
GENETICS, SO AGAIN, JUST FROM
THE SIMPLE CONCEPT, AN ANCESTOR
IS SOMEONE FROM WHOM A PERSON IS
DESCENDED BUT IT IS IMPORTANT TO
KNOW THAT MOST PEOPLE DO NOT
HAVE COMPREHENSIVE INFORMATION
ABOUT YOUR ANCESTORS BEYOND
FUTURE GENERATIONS AGO.
THERE'S ALSO THE CONCEPT OF
NEUROLOGICAL ANCESTORS OR
ANCESTRY AND THAT IS WHAT YOU
TEND TO HEAR MORE ABOUT AND THAT
BASICALLY REP SESENTS ANYONE IN
YOUR FAMILY TREE OR IN YOUR
FAMILY TREE THAT YOU DRAW.
[INDISCERNIBLE] IDENTIFIABLE,
IDENTIFIABLE OF THE ANCESTORS IN
YOUR FAMILY TREE.
THE CONCEPT I WILL TALK MORE
ABOUT TODAY IS THE CONCEPT OF
GENETIC ANCESTORS AND/OR
GENERATED ANCESTRY.
WHICH IS A BIOLOGICAL ANCESTOR
FROM WHOM YOUR DNA WAS DIRECTLY
INHERITED, SO THAT'S A
DISTINCTION SO ANCESTRY IS A
SUBSET OF GEANIO LOGICAL
ANCESTORS.
THE PROBABILITY OF THAT A GEANIO
LOGICAL ANCESTOR IS A GENETIC
ANCESTOR DECREASES AS GENERATION
PASSES AS YOU WILL IMAGINE.
I WILL SAY THAT WHAT WE ACTUALLY
MEASURED AND WHAT WE COLLECT DNA
FROM INDIVIDUAL TO UNDERSTAND
DISTRIBUTION OF ANCESTRIES
AROUND THE WORLD IS WHAT IS
REFERRED GENETIC SIMILARITY.
HERE WE MEASURED THE ALLELE
FREQUENCIES OR HAPLOTYPE
FREQUENCIES THAT WE OBTAIN FROM
INDIVIDUALS, AND WE DO THAT IN
THE ANALYSIS OF CONTEXT
REFERENCE GENOMIC DATABASE OR
DID THEA BASES, AGAIN THE
QUESTION OF REFERENCE IS REALLY
IMPORTANT AND I WILL COME BACK
TO IT DURING MY TALK.
SO THIS DEFINITION OF GENETIC
SIMILARITY IS WHAT WE REALLY
TALKED ABOUT WHEN WE USE STATUS
QUO GENETIC SOFTWARE SUCH AS
ADMIXTURE TO REPORT INFORMATION
TO INDIVIDUALS.
AND IT IS ALSO WHAT YOU GET WHEN
YOU SEND YOUR DNA TO SOME OF
THESE DIRECT TO CONSUMERS
COMPANIES LIKE 23 AND ME OR MY
HERITAGE.
SO THE CONCEPT OF ANCESTRY, YOU
HEAR THINGS LIKE WHERE IN THE
WORLD WERE YOUR ANCESTORS FROM?
AND THE THINKING HERE IS THAT BY
PROVIDING THE DNA IS A TRUE
SURVIVOR O TRUE BY PROVIDING
BLOOD SAMPLES WHERE DNA IS
EXTRACTED FROM, WE CAN USE
STATISTICAL METHODS TO CLUSTER
THE DIFFERENT PARTS OF YOUR
GENOME AND TO BE ABLE TO MAKE
INFERENCE ABOUT WHERE YOUR
ANCESTORS THAT WE CAN IDENTIFY
THROUGH YOUR DNA, ACTUALLY COME
FROM AND SO, YOU WILL NOT BE
SURPRISING WHEN THEY GIVE YOU
PERCENTAGES LIKE ENGLISH IS 50%,
SCANDINAVIAN 20%, YOU KNOW, ET
CETERA.
NOW IT IS IMPORTANT THAT THE
REFERENCE THAT USED FOR ALL OF
THIS TYPE OF ANALYSIS CAN INDEED
INNERFLU ENSEL THE RESULT THAT
YOU GET AND THAT RESULT THAT YOU
GET CAN INDEED CHANGE AS YOU
CHANGE IN THE REFERENCE
POPULATIONS OR AS WE IMPROVED
REFERENCE POPULATIONS BY DOING
MORE DIVERSE GENETICS AROUND THE
WORLD.
SO THAT IS REALLY IMPORTANT TO
HAVE IN MIND.
SO IN MY GROUP, AGAIN, AT THE
NIH HERE, THIS WORK LED BY
[INDISCERNIBLE] IN MY GROUP,
DOES A LOT OF OUR POPULATION
GENETICS WORK, IS REALLY BASED
ON THE FACAS ACCOUNT THAT WE
WANTED TO UNDERSTAND HOW
ANCESTRY IS CLOSEST AROUND THE
WORLD.
FIRST OF ALL IF WE LOOK AT
GLOBAL POPULATIONS HOW MANY
ANCESTRIES ON DO WE SEE AND DOES
THAT CORRELATE WITH OUR
UNDERSTANDING OF LANGUAGE GROUPS
AROUND THE WORLD.
SO WE USED--WE PUT TOGETHER
ABOUT 6000 INDIVIDUALS FROM
AROUND THE WORLD AS YOU SEE IN
THIS PICTURE HERE, THIS GLOBAL
MAP FROM 30 PRIMARY LANGUAGE
FAMILY GROUPS FROM PLACES ALL
OVER THE WORLD AND WE BASICALLY
IGNORE [INDISCERNIBLE] ANCESTORS
AND THE ETHNICITY OR SOME PEOPLE
MAYBE WILL USE THE CONCEPT OF
RACE AND BASICALLY ASK OUR
COMPUTER A STATISTICAL SOFTWARE
PROGRAM TO CLUSTER PEOPLE USING
THE GENETIC INFORMATION THAT WE
HAVE.
AT THE TIME WE DID THIS STUDY,
IT WAS THE [INDISCERNIBLE]
ASSAYS IN THE WORLD AND WHAT DID
WE SEE?
ONE OF THE MOST IMPORTANT POINTS
I WANT TO MAKE IN MY
PRESENTATION TODAY IS HOW COMMON
AND HOW COMPLEX ANCESTRY IS.
WHEN WE LOOK AT DIFFERENT
CONTINENT, WE SAW THAT EACH
CONTINENT HAD MULTIPLE
ANCESTRIES AND THAT THERE'S NO 1
CONTINENT WHERE YOU GO AND YOU
WILL ONLY SEE YOUR ANCESTRY SO
WE HAVE THE COMBINATIONS EACH
LINE OF THIS CARTOON HERE REALLY
DOES REPRESENT AN INDIVIDUAL
TRYING TO [INDISCERNIBLE] HERE.
SO IF YOU LOOK AT EACH LINE, A
SOLID LINE, SO IT'S THE
COMPLEXITY OF ANCESTRIES AND
MIXTURE, SO--BUT IN TERMS OF THE
RESULT, ACTUALLY IS THAT WE'RE
ABLE TO USE STATISTICAL PROGRAM
TO OBSERVE OUR ANCESTORS
GLOBALLY, SO A LEVEL OF THOSE IN
AFFRIC AWITH THE DIVERSITY OF
POPULATIONS AND I WILL TALK
ABOUT THAT MORE IN A MINUTE IF
YOU DON'T TAKE ANY MESSAGE FROM
OUR TALK TODAY, THIS IS REALLY
THE KEY, THAT THE MAJORITY OF US
AND THIS DATA SET HAVE MIXED
ANCESTRY 93.7% OF INDIVIDUALS IN
THIS GLOBAL DATA SET HAVE MIXED
ANCESTRY AND INDIVIDUALS HAVE AN
AVERAGE OF 4 ANCESTRIES AND
HUMAN ANCESTRY IS VERY WELL WITH
LANGUAGE GROUP BECAUSE 1 OF THE
BARRIERS ON SHARING DNA AGAINST
IS LANGUAGE.
AND WE ALSO NOTE THAT THE WAY WE
DESCRIBE OURSELVES USING CONCEPT
OF RACE REALLY IS NOT AN
OBJECTIVE GENOMIC CLASSIFIER AND
I WILL SPEAK A LITTLE MORE ABOUT
THAT.
NOW WHAT IS THE TAKE HOME OF
THIS WORK?
HISTORY AND HELT.
AND BECAUSE WE ARE USING DNA TO
DEFINE ANCESTRIES, ANCESTRIES
THEREFORE SUBJECT TO
EVOLUTIONARY CHANGE AND THAT IS
ANCESTRIES ARE INFLUENCED BY
BIRTH AND DEATH CYCLES AND
ANCESTRY CAN THEREFORE VARY AND
CHANGE OVER TIME SO AGAIN VERY,
VERY IMPORTANT CONCEPT.
SO ALL OF THIS WHEN IT COMES TO
THE CONCEPT OF PRECISION
MEDICINE AND HISTORIES AND
GENETIC SYSTEM THE CONCEPT OF
GENETIC VARIATION AND THAT IS AS
A RESULT OF SEQUENCING THE HUMAN
GENOME, IN THE LAB AND A
THOUSAND GENOME AND SUBSEQUENT
STUDIES AFTER THAT WE HAVE BEGAN
TO APPRECIATE THE FACT THAT THE
DISTRIBUTION OF HUMAN GENETIC
VARIATION IS NOT RANDOM, THERE
IS STRUCTURE IN THERE, AROUND
IT, AND THIS QUALITY OF
INDIVIDUALS, ALL FAMILIES,
ANCESTRIES OR GEOGRAPHY AND THE
FACTORS THAT DRIVE THESE
DIFFERENCES INCLUDES THINGS LIKE
ANDROGEN ORDER OF MICRONS
GENETIC DRIFT, ADAPTATION, AGAIN
DUE TO CLIMATE, INFECIOUS
AGENTS, [INDISCERNIBLE] AND
ENVIRONMENTAL TOXINS AND I WILL
SHOW EMPLOY ANDS OF THAT.
BUT TO TAKE US REALLY BACK TO
WHERE WE ALL CAME FROM AND THAT
IS, IT IS PRETTY CONCESTENT, NOW
I DON'T THINK WE GET TOO MUCH
ARGUMENT ABOUT THE FACT THAT
HUMANS ORIGINATED IN AFRICA,
SOME 300,000 YEARS AGO AND FROM
THERE, A SUBSET MIGRATED TO
POPULATING REST OF THE WORLD.
IT IS BECAUSE OF THIS COMMON
HISTORY, [INDISCERNIBLE]
HISTORY, THAT WE ALL SHARE OVER
99% OF OUR GENETIC INHERITANCE.
AND HUMAN BEINGS HAVE LIVED ON
THE AFRICAN CONTINENT AND THAT
HAVE [INDISCERNIBLE] OF THE
GENOME FOR THE AFRIRK ANS.
SO WE ARE VERY SIMILAR BUT THERE
ARE DIFFERENCES, 1 OF THE%
ORIGINAL DIFFERENCES, I CALL IT
ORIGINAL DIFFERENCE IS WHEN DO
SUBSETS OF INDIVIDUALS, OF
COURSE, WHO MIGRATED OUT OF
AFRICA TO POPULATE THE REST OF
THE WORLD, WHEN THEY LEFT, THEY
ONLY TOOK A SUBSET OF GENETIC
VARIATION THAT EXISTED IN AFRICA
AT THAT POINT AND THEREFORE IT
IS ONLY IN AFRICA THAT YOU CAN'T
REALLY STUDY SOME OF THOSE
GENETIC VARIATION THAT WAS LEFT
BEHIND.
AND IN THAT WAY, I TRIED TO
REPRESENT THE DIVERSITY OF
AFRICAN GENOMES AND THE
DIFFERENCES BETWEEN AFRICAN
POPULATIONS IS REALLY WHEN YOU
TAKE THIS EUROPE AND
[INDISCERNIBLE] AND YOU COMPARE
THEM TO EACH OTHER, THEY ARE
MORE LIKELY TO BE DIFFERENT TO
EACH OTHER WHEN YOU COMPARE THEM
TO THIS INDIVIDUAL GUY, SO WE
SORT OF BRING TO THE QUESTION,
WHEN IT COMES TO GENETICS
WHETHER YOU SAY AFRICAN, YOU
NEED TO BE EXTREMELY CAREFUL AND
YOU HAVE TO BE CLEAR AND BE
SPECIFIC ABOUT WHAT YOU'RE
ACTUALLY TALKING ABOUT.
AND AGAIN, I WILL SHOW THE
IMPLICATIONS OF THAT AS GIIVE BY
TALK.
SO AS A RESULT OF THAT LONG
EVOLUTIONARY HISTORY OF AFRICAN
PEOPLE AND AFRICAN GENOMES AND
THAT THE DISTRIBUTION OF
VARIATIONS AROUND THE WORLD
ACTUALLY IS NOT RANDOM, WHAT YOU
DO SEE IS THAT THE NUMBER OF
VARIABLE SIZE BY GENOME AS
REPORTED BY THE THOUSAND GENOME
PROJECT YOU SEE THAT AFRICAN
POPULATIONS, DISPLAY THE HIGHEST
NUMBER OF VARIABLE SIZE BY
GENOME FOLLOWED BY THE AMERICAS
EAST ASIANS AND EUROPEONS AND
THIS CAN INCLUDE VARIATION, A
SINGLE POLYMORPHISM OR SNPs,
OR [INDISCERNIBLE] LOSS OF
FUNCTION VARIANTS SO IN THIS YOU
SEE MORE MOBILITY IN AFRICAN
POPULATIONS AND SIMPLY HAPPENS
IN THE TYPE OF THE HAPLOTYPE
STRUCTURE WHICH REFERS TO HOW TO
TRAVEL TOGETHER IN THE GENOME
BECAUSE THE AFRICAN GENOMES HAVE
MORE TIME TO VALID AND RELIABLE
EXPE THEREFORE TENDS TO MORPH
THAT METHOD SX HEAT THAT CAN BE
A VERY FINE TOOL FOR LOCALIZING
GENES AT THE POPULATION LEVEL
AND I WANT TO SHOW AN EXAMPLE OF
THAT FROM [INDISCERNIBLE] OF MY
GROUP AT THE NIH.
SO THIS IS THE VIDEO SHOWING
THE--I'M TRYING TO GET BACK, SO
I WILL PLAY THIS VIDEO TO SHOW
HOW WE USE THE AFRICAN GENOME TO
FINE MAP A LOCI TO HEAR ABOUT
THE AFRICAN VARIANT.
>> THIS GROUP DR. ROTIMI'S
GROUP, IDENTIFIED GENETIC
ARCHITECTURE OF CIRCULATING
RESISTANT LEVELS IN AFRICANS
FROM NIGERIA, KENYA AND GANNAA
AND AFRICAN AMERICANS FROM THE
WASHINGTON D. C. AREA.
RESISTIN IS A SMALL PEPTIDE
SECRETED BY BONE MARROW IN
HUMANS AND IT'S BEEN SUGGESTED
AS A BIOMARKER FOR DIABETES.
IDENTIFYING SIGNIFICANT
ASSOCIATIONS WITH GENETIC
VARIANTS, THE GENE THAT INKEDS
RESISTIN, DR. ROUGH ATOM OTIMI'S
GROUP CONDUCTED A STUDY USING
18 MILLION MARKERS IN
[INDISCERNIBLE] AFRICANS AND
2000 AFRICAN AMERICANS
SEPARATELY.
BOTH GWAS IDENTIFIED THE SAME
VARIANT, 75 KILOBASES UPSTREAM
OF THE RTN GENE AS THE MOST
SIGNIFICANTLY ASSOCIATED SNP.
THE POPULATIONS ALLOWED THE
RESEARCHERS TO DEFINE THIS
LOCUST TO A SINGLE VARIOUS AND
WHOLE EXOHM SEQUENCING STUDIES
ROLLED OUT THE CONTRIBUTIONS OF
CODING IN THE RTN GENE, FURGTSER
THE GTEX DATA SET DEMONSTRATED
ETL OF THE GENE EXPRESSION IN
IMMUNE CELLS, TOGETHER THESE
RESULTS SUGGEST THAT THE
VARIANTS THAT AFFECT RESISTANT
EXPRESSION LEVELS DERIVE THE
VARIATION OF PLASMA RESIST APT
LEVELS.
FINALLY THE AUTHORS PERFORMED
ANALYSIS OF METABOLIC
PHENOTYPES.
HOWEVER THEY DID NOT FIND
EVIDENCE OF A CAUSAL ASSOCIATION
BETWEEN RESISTANT LEEVERLS AND
METABOLIC SYNDROME RELATED
PHENOTYPES.
OVERALL THIS STUDY WAS ABLE TO
FIND LOCUST FOR THE ASSOCIATIONS
AND PERHAPS MORE INTERESTINGLY
CAST DOUBTS ON THE IDEA OF
RESISTIN AS A BIOMARKER FOR TYPE
2 DIABETES.
>> THANK YOU VERY MUCH, AGAIN
TAKING ADVANTAGE OF THE OF THE
POPULATION POPULATIONS AND TO
FINE MAP THE LOCUST IN THE
GENOME ANOTHER DEMONSTRATION OF
WHY AGAIN THIS IS REALLY
IMPORTANT FOR US TO ENGAGE
DIFFERENT ANCESTRY BIOGRAMS AND
WHERE WE DEPLOY GENETICS AND
GENOMICS AND AND GO TO PRECISION
MEDICINE IS ALSO ILLUSTRATED IN
THIS WORK THAT WE'VE BEEN DOING
IN AFRICAN COUNTRIES AND
[INDISCERNIBLE], GANNAA AND
KENYA, THE FIRST PINTIE WANT TO
MAKE SHER IS THAT USING GENOME
WIDE ASSOCIATION STUDY IN ABOUT
A MILLION GROUP IN ANCESTRY
INDIVIDUALS WE HAVE BEEN
MATERIALLY VERY PRODUCTIVE IN
IDENTIFYING LOCI FOR TYPE 2
DIABETES, AND DELIVER 400 LO CI
SO FAR, SO THUS BY THESE
INDIVIDUALS WHO ARE STILL ABLE
TO IDENTIFY LOCUST IN
POPULATIONS IN THE CONCEST OF
DIABETES IN THIS WORK WE'VE BEEN
DOING FOR THE PAST 20 YEARS
ACROSS THE AFRICAN COUNTRIES.
WE IDENTIFIED THIS VERY
INTERESTING WORK AND 0 AND
BETWEEN THAT WAS ASSOCIATED WITH
TYPE 2 DIABETES AND THE ZRAN B3
ASSOCIATED VARIANTS WAS COMMON
IN AFRICAN ANCESTRY OF
POPULATIONS OF VERY RARE SUBSET
IN NONAFRICAN POPULATIONS.
AND WE WENT FOR THEIR USING THIS
TO TRY TO UNDERSTAND HOW THESE
GENE IMPACTS, YOU KNOW TYPE 2
DIABETES AND 1 THING WE NOTICED
WAS THAT WHEN WE KNOCKED DOWN
ZRANB3, THERE WAS A MASSIVE
REDUCTION IN BETA CELLS, THIS IS
THE CONTROL AND THIS IS IN THE
KNOCK DOWN IN ZEBRA FISH.
SO AGAIN DEMONSTRATING THE
IMPACT OF [INDISCERNIBLE] AND
MORE IMPORTANTLY IN THE
MAMMALIAN CELL LINES, WE WERE
ABLE TO ASSURE THAT THAT
SUPPRESS ANDROGENS WERE RELEASED
TO THAT ARE SILENCED IN THE
ENVIRONMENT WHICH BEGIN TO
DEMONSTRATE TO US, OR HOW IT
IMPACT TYPE 2 DIABETES RISK IN
THE SECRETION PROCESSES AND
RESPONSE TO GLUCOSE ENVIRONMENT,
SO THAT WAS AGAIN SOMETHING THEY
WAS REALLY, REALLY EXCITING TO
TAKEN ADVANTAGE OF DIFFERENT
ADVERSITY IN THESE POPULATIONS
IN THIS PARTICULAR INSTANCE.
THIS IS AN EXAMPLE, AGAIN WORK
LED BY [INDISCERNIBLE] AND
[INDISCERNIBLE] IN MY LAB, WHERE
WE IDENTIFY NOVEL VARIANT FOR
OBESITY IN WEST AFRICA, AND
REPLICATED IN THE WORK IN ALMOST
10,000 AFRICAN AMERICANS AND IN
THE SEMA4 D GENE, THAT WAS IN 1%
IN THE WEST AFRICANS AND AFRICAN
AMERICANS AND BUT WHAT WAS
INTERESTING IS THE CARRIER
ALLELE, WHERE IT WAS 6-POUNDS
HEAVIER THAN NONCARRIERS WHICH
IS ABSOLUTELY SIGNIFICANT WITHIN
THE DIFFERENCE IN WEIGHT AT A
POPULATION LEVEL.
WE WERE ABLE TO SHOW PERSONAL
LEVEL OF SIGMA 4 D, VARYING BY
OBESITY STATUS SO THESE ARE ARE
NONBASED AND WHEN WE COMBINE THE
DATA, AGAIN, THIS DISCOVERY
POSSIBLY ANCESTRY OR ASIAN
POPULATIONS BECAUSE THE VARIANTS
AND MONOMORPHIC IN THIS ANCESTRY
GROUPS.
IN THAT WORK LED BY ED RAMS ON
WHO IS AT THE CENTER, BUT WAS A
POST DOC IN THE CENTER AND WHEN
WE DID THIS WORK, WE SHOWED THAT
IN THE IMPORTANT THAT WE
DIFFERENT POPULATIONS AND
ANCESTRY BACKGROUNDS BECAUSE IN
THE VALID AND RELIABLE YABTS
THAT MAYBE IMPORTANT IN THE
DETERMINANT IN THIS INSTANCE IT
WAS THE WARFORIN, MAY NOT BE
DISTRIBUTED AROUND THE WORLD AND
1 EXAMPLE IS THIS HAPLOTYPE,--SO
THIS HAPLOTYPE TCHGC, THAT WE
DID NOT SEE IN NONAFRICAN
POPULATION WAS QUITE COMMON IN
AFRICAN POPULATIONS PASS IMPACT
ON WOR FORIN INDUCING WHICH WE
SHOULD AGAIN NOT CURRENTLY
ADEQUATELY REPRESENT INDEED HOW
WE DO WAR FORIN, SO WE PUT
INTOLET IMPORTANCE OF DOING THIS
KIND OF WORK, SO IT'S
UNDERSTANDING THE PRESSURE
RESPONSE TO DRUGS THIS IS 1 OF
THE BEST EXAMPLE THAT I CAN
REALLY SHOW TO YOU AND THIS IS A
PAPER THAT WAS PUBLISHED TO MY
FRIEND LYNN JORDE, IN 2010 WITH
WHERE WE SHOWED CLEARLY THAT THE
HLA MARKER, THE NEGATIVE PREDICT
ADVERSE REACTION TO ABACAVIR
TREATMENT, SPECIALLY IN HIV THAT
IT DOES HELP TREMEWOOUSLY AROUND
BUT WHEN I WANT TO
POINT OUT WHEN YOU LOOK AT
INDIVIDUALS YOU MAY CALL AFRICAN
THAT THE VARIATION, IT IS VERY,
VERY DIFFERENT FROM AMONG THE
[INDISCERNIBLE], THEY HAVE 1 OF
THE HIGHEST RATES IN THE WORLD
WHERE IT'S ALMOST 0 AMONG THE
[INDISCERNIBLE] AND AFRICAN AND
AMERICANS IT'S 1% SSO THE
QUESTION IMENT TO MAKE IS THAT
USING [INDISCERNIBLE] LIKE BLACK
OR AFRICAN IS RADICALLY
DIFFERENT FREQUENCIES OF VERY
IMPORTANT VARIANT ARK ROUND THE
WORLD AND CAN LEAD TO 1 PUBLIC
HEALTH DECISIONS BY NOT
ADEQUATELY UNDERSTANDING THIS
DISTRIBUTION OR LOOKING AT
SOMEBODY FROM THE VERY
PHENOTYPIC POINT OF VIEW.
SO AGAIN, AS WE MOVE THROUGH
PRECISION MEDICINE WE NEED TO BE
VERY, VERY CONSCIOUS OF THESE
KINDS OF FINDINGS AND THAT'S
ALSO A VARIATION THAT WE SEE IN
TERMS OF ANCESTRAL BACKGROUND
THAT IS VERY IMPORTANT FOR US TO
TAKE INTO CONCENTRATION AS THE
ECONOMIC MEDICINE IS THE
EPITHELIALIGRATION AND
ESPECIALLY IN THIS CASE
[INDISCERNIBLE] PROGRESSION.
IT IS NOW VERY CLEAR THAT
SOMEWHERE AFTER THE ERA OF
AFRICAN MIGRATION THAT THE
POPULATIONS IN EUROPE AND ASIA,
IT WAS THE CONCEPT OF
INTEGRATION, WITH ANOTHER
TELOMERE SHORTENING AND THAT
[INDISCERNIBLE] THAT WERE
PRESENT IN THAT PART OF THE
WORLD AND A QUESTION THAT WAS
IMPORTANT FOR US TO ASK IS DID
THE REGION OF THESE INDIVIDUALS
IMPORTANT IN TERMS OF HELT AND
ALL THAT TRAITS.
AND I WANT TO SHOW YOU EXAMPLES
OF THAT AND I WILL USE EXAMPLES
TO DEMONSTRATE THAT, THIS IS FOR
TYPE 2 DIABETES, SO WHEN YOU
LOOK AT THIS WORK THAT WAS
ELEGANT WORK THAT WAS TYPE 2
DIABETES CONSORTIUM, ARE LOOK
BEING AT POPULATIONS DOING GWAS
AND IF I FIND SIGNIFICANT SIGNAL
AND SOME SORT OF CARRIER, IN THE
SLC 16A 11 AND THE FREQUENCY OF
THIS CARRIER OF ABSOLUTELY MUCH
HIGHER AMONG INDIVIDUALS OF
NATIVE ANCESTRY WAS ABOUT 10% IN
AGENTS AND RARE EUROPEAN
POPULATION.
BUT THE POINT I WANT TO MAKE
HERE IS WHEN THIS HAPLOTYPE WAS
TRACED BACK USING SEQUENCING IT
BECAME QUITE CLEAR THAT THE
HAPLOTYPE HAD PROGRESSED INTO
MODERN HUMANS WITH THE ADMIXTURE
WITH NEANDERTHALS AND THAT 2-4%
OF THE NEUROECTODERMAL ANDIE
THAT WILL IS THE GENOME WE SEE
PRESENTED IN THE GENOME
POPULATIONS MAY INDEED HAVE
BIOLOGICAL SIGNIFICANCE AND THAT
WE NEED TO PAY ATTENTION TO IT.
THIS IS MORE RECENT EXAMPLE
SHOWING SAME [INDISCERNIBLE] BUT
IN THE CONTEXT OF COVID.
THIS WAS THE POPULATION IN THE
JOURNAL OF MEDICINE, IN 2020
THAT SHOWS A VERY STRONG
CHROMOSOME 3 FOR COVID
SUSCEPTIBLE AND WHAT WAS
INTERESTING FTION THAT GROUPS
THAT DON'T [INDISCERNIBLE] IN
THE WORLD DEMONSTRATE THAD THIS
SIGNATURES MENTORSHIP SKILL IN
THE CHROMOSOME 3 WAS INDEED
INHERITED FROM NEUROECTODERMAL
ANDIE THAT WILL AND THAT ABOUT
50% SOUTH ASIA AND 16% EUROPEAN,
AND STRONGLY ASSOCIATED WITH
SEVERE COVID INFECTION AND
HOSPITALIZATION AND THEN THERE
WAS SPECULATION THAT THE HIGHER
FREQUENCY OF THIS GENOMIC REGION
IMPRESSES OF THE ANCESTRY MAY
HAVE EXPLAINED THEIR 2 TIMES
MORTALITY FROM COVID COMPARED TO
THE GENERAL UK POPULATIONS,
AGAIN THESE ARE STUDIES THAT ARE
ONGOING BUT BEGINNING TO SHOW US
TO US AGAIN, HOW DOES
INTEGRATIONS AS PART OF THE
GENOME NEEDS TO BE STUDIED IN
TERMS OF BIOLOGICAL FUNCTIONS.
SO THIS IS THE--THIS HAS BEEN
WHAT OOIVELGTS IN THE
DISTRIBUTION OF HUMAN GENETIC
VARIATION AND IN THIS CASE, AX
DATA PROTECTIONIVE CAPABILITY
FOR SPECIFIC TOXIN.
THIS IS WHEN I READ THIS PAPER I
WAS ABSOLUTELY TAKEN BACK BY IT.
THE FACT THAT IT WAS A SMALL
VILLAGE IN ARGENTINA THAT THE
GROUND WATER IS CONTAMINATED
WITH ARSENIC, OVER 20 TYPES
ACCEPTABLE LEVEL AND IT LOOKS
LIKE THIS LOCAL POPULATION HAVE
INDEED ADAPTED TO THIS POISON
EECT OF ARSENIC BY HAVING THIS
[INDISCERNIBLE] PROCESS THAT
ALLOWED IT TO METABOLIZE THE
TOXIN INTO A LESS TOXIC
MOLECULE, YOU KNOW AGAIN
SUGGESTING VERY STRONG POSITIVE
SELECTION IN THIS GROUP.
WHAT WAS ACTUALLY INTERESTING TO
ME IS THAT THE SURROUNDING
VILLAGE THAT WERE NOT EXPOSED TO
ARSENIC HAD LITTLE OR NO
FREQUENT INCREASE IN PREQUENCY
OR THIS PARTICULAR HAPLOTYPE
THAT IS HELPING INDIVIDUALS IN
IN VILLAGE TO BE ABLE TO LIVE IN
AN ENVIRONMENT THAT IS
CONTAMINATED BY ARSENIC.
SO, WE SO SINCE THIS IS LIKELY
POSITIVE SELECTION SINCE IT'S
EMBEDDED IN THE HAPLOTYPE OF
THIS GROUP AND AT MORE HIGH
FREQUENCY THAN IN THE COMMUNITY,
AND I BELIEVE THAT THIS IS THE
FIRST EXAMPLE HUMAN ADAPTATION
TO THE ENVIRONMENT, AGAIN
EMPHASIZING THE IMPORTANCE OF
STUDYING THE DIFFERENT
ANCESTRIES AROUND THE WORLD AND
DIFFERENT POPULATIONS, AS WE
DEPLOY--TRY TONED THE BIOLOGY OF
OUR GENOME OF VARIOUS DISEASES
AND OUTCOMES.
NOW I WILL USE THE AFRICAN DIAS
PARATO MAKE ADDITIONAL POINTS
ABOUT THE IMPORTANCE OF ANCESTRY
AND 1 OF THE THINGS THAT THAT
WAS A RESULT OF THE SLAVE TRADE,
TO THIS, ALL THE WAY TO AREAS OF
AN GOALA WERE FORCED ENSLAVED
AND FORCED TO GO TO DIFFERENT
PARTS OF THE WORLD AND START
AMERICA AND EUROPE.
WHAT THAT DID WAS CREATE A
VARYING DEGREESS OF MIXTURE THAT
WE SEE IN PRESENTING POPULATIONS
WHETHER IT'S IN THE CARIBBEAN OR
AMERICANS IN THE U.S. OR YOU
KNOW INSIDE AMERICA.
SO WHETHER YOU SEE IT LIKE THE
CARTOON I SHOWED EARLIER, EACH
OF THESE LINES HERE, THAT YOU
SEE ARE INDIVIDUALS AND AGAIN AS
YOU CAN SEE, THERE'S NO SOLID
LINE, THIS IS WHOLE ADMIXTURE
INDIVIDUAL, BUT VARYING DEGREE
OF ADMIXTURE.
SO FOR EXAMPLE, WHEN YOU LOOK AT
INDIVIDUALS FROM PERU, YOU SLEEP
APNEA AND OBESITYY A VERY HIGH
LEVEL OF NATIVE AMERICAN
ANCESTRY COMPARED TO FOR
EXAMPLE, INDIVIDUALS FROM THE
CARIBBEAN.
AND BUT THE POINT I WANT TO MAKE
IS AS A RESULT OF ANCESTRY, IT
IS IMPORTANT THAT WE DO NOT
ASSUME THAT HAVE THE SAME
GENETIC BACKGROUND OR SAME
ANCESTRY BACKGROUND AND BECAUSE
WE LOOK AT THIS MIXTURE, IT
VARIES FROM 0 TO ALMOST CLOSELY
100% AND IN THE RIDGE OF NATIVE
AMERICAN ANCESTRY ALSO COVER
THIS BROAD SPECTRUM.
SO AGAIN, BRING INTO QUESTION,
WHEN WE SAY AFRICAN AMERICAN,
WHO ARE WE REFERRING TO AND I
WANT TO USE THIS EXAMPLE AGAIN
TO MAKE THAT POINT EVEN
STRONGER.
WOVEN OF THE THINGS IS FOR
WHATEVER REASON, AFRICAN
AMERICANS HAVE MUCH MORE MORE ON
THE TRIGLYCERIDE LEVEL SHOULD
HAVE A DIET THAT SHOW OTHERWISE,
SO IF YOU LOOK AT THIS RATIO,
THEY ARE MUCH LOWER AND IF YOU
LOOK AT THIS HERE, THEY ARE
HIGHER, AND IF YOU PLOT THE
LEVEL OF TRIGLYCERIDES AGAINST
THE PROPORTION OF AFRICAN
ANCESTRY, YOU SEE THAT
TRIGLYCERIDE GO DOWN AS THE
AFRICAN ANCESTRY INCREASES AND
HDL GOES UP, SO WE WERE CURIOUS
IN THAT LAB, AGAIN, WORK LED BY
[INDISCERNIBLE], AND WE
SEQUENCED 5 GENES THAT WERE
IMPLICATED IN BIOCHEMISTRY AND
WITH THE WORK THAT WE ARE DOING
IN THE AFRICAN POPULATION IN
THIS AREA, BUT THE POINT I WANT
TO MAKE HERE IS THE
[INDISCERNIBLE] SNP.
ONE WE SERVED WHICH WAS
WONDERFUL FOR US AND WE ARE
EXCITED ABOUT THIS FINDING IS
THAT THE LEVEL OF TRIGLYCERIDES
AND HDL VARIES QUITE
TREMENDOUSLY AMONG AFRICAN
AMERICAN SO FOR EXAMPLE, WHEN
YOU SEE AN AFRICAN AMERICANS WHO
HAVE 2 COPIES OF THE
[INDISCERNIBLE] AT THESE LOCUST,
THEY DO HAVE TRIGLYCERIDES ON
EACH LEVEL THAT ARE SIMILAR TO
THAT OF WEST AFRICANS BUT WHEN
THAT BAR GRAM IS EUROPEAN AND
SEE THE AFRICAN AMERICANS THEY
DISPLAY LIPID LEVELS THAT ARE
SIMILAR TO THAT OF EUROPEAN.
AGAIN, GIVING US CAUTION WHEN WE
SAY AFRICAN AMERICAN THAT MAKE
SURE THAT WE ARE NOT
OVERGENERALIZING AND YOU KOOBT
ASSUME THAT YOU SEE FROM THE
FIELD REPRESENTS LARGER AFRICAN
AMERICAN GROUP AND ANOTHER THING
WE HAVE DONE IS USE ADMIXTURE
MAPPING WHICH IS BASICALLY
TAKING ADVANTAGE OF THE FACT
THAT WE HAVE 2 POPULATIONS IN
TERMS OF OUR EXAMPLE WHO HAVE
YIER ANS AND AFRICANS AND
MARRIED AND SHARED DNA AND WITH
GENERATIONS WE HAVE DIFFERENT
DISTRIBUTIONS FOR WHAT WE CALL
LOCAL ANCESTRIES AND YOU CAN USE
THE MAP TO TRY TO FIND THE
REASON WHY YOU SEE FREQUENCY
BEHIND THE DISEASE COMPARED TO
SAY THE CONTROLS AND I WANT TO
DEMONSTRATE THIS USING THE WORK,
THE WORK VERY IMPORTANT WORK IN
KIDNEY DISEASE IN AFRICAN
AMERICANS.
SO JUST TO REVIEW THE
EPIDEMIOLOGY, AFRICAN AMERICANS
ARE 13% OF THE U.S. POPULATION
BUT THEY ACCOUNT FOR 32% OF
KIDNEY FAILURE IN THE U.S., AND
THEY ARE 4 TIMES MORE LIKELY TO
DEVELOP KIDNEY FAILURE THAN
THEIR EUROPEAN COUNTERPART.
SO A GROUP FROM NIH AND HOPKINS
DEVELOP--TO SAY IF INDEED THAT
THESE DIFFERENCES IN KIDNEY
DISEASE IS DUE TO GENETICS,
GENETIC BACKGROUND, THAT YOU SEE
THE HIGH FREQUENCY YOU WILL
START AGAINST THE EUROPEAN GENE
POOL.
SO THEY USE ADMIXTURE MAPPING
AND THEY'RE AGAIN JEFF
[INDISCERNIBLE] AND LINDA
[INDISCERNIBLE] WHO IS
UNFORTUNATELY NO LONGER WITH US,
DID THIS ELEGANT WORK, TO SEE
THE VARIOUS SIGNAL OF
[INDISCERNIBLE], AND 22 THAT WAS
LATER SHOWN TO BE INDEED YOU
KNOW WAS TRACKING
[INDISCERNIBLE] 1 IN TERMS OF
LINKAGE [INDISCERNIBLE].
BUT WHAT WAS IMPORTANT WITH IT
FIEBDING WAS THAT INDIVIDUALS
WHO CARRY 2 COPIES OF THE APOL1
VARIANT HAVE END STAGE DISEASE
AND THE FREQUENCY WAS ABSOLUTELY
HIGHEST IN WEST AFRICA AND ABOUT
20% IN AFRICAN AMERICANS AND
ABSENT IN EUROPEAN AND ASIANS.
THIS WAS ABSOLUTELY A WONDERFUL
FINDINGS AND ALSO SURPRISING
BECAUSE WHEN THINGS ARE THIS
DELETERIOUS, THE EVOLUTIONARY
PROCESS TEND TO REMOVE THEM
UNLESS THEY CAN FIND SOME
ADVANTAGE.
AND IT TURNS OUT THAT THIS AREA
THAT IS VERY DANGEROUS, FOR
KIDNEY DISEASE, ABSOLUTELY
PROTECT YOU BECAUSE THEY
[INDISCERNIBLE] THAT ARE
RESPONSIBLE FOR WHAT WE CALL THE
AFRICAN SLEEPING SICKNESS WHICH
IS MORE LIKELY TO KID YOU BEFORE
KIDNEY DISEASE IN AREAS WHERE IT
IS INDEMMIC SO YOU CAN SEE WHY
THE EVOLUTIONARY PROCESS WILL
SELECT THIS PROCESS AND NOTE
THAT IS DANGEROUS WHEN YOU
[INDISCERNIBLE] OF YOUR KIDNEY.
AND WHAT IT HAS DONE IS TO HELP
US EXPLAIN DISPARITY, NOT ALL OF
IT, SO 1 IN 5 PLACES OF PERFECT
[INDISCERNIBLE], YOU KNOW THE
AFRICAN AMERICANS, WITH 2 COPIES
OF THIS VARIANT ARE RESPONSIBLE
FOR THE RISK IN TERMS OF KIDNEY
DISEASE.
SO SENCHT% OF NONDIDN'TIC KIDNEY
DISEASES IN [INDISCERNIBLE],
AFRICAN AMERICANS IS DUE TO SWRG
2 COPIES OF THIS VARIATION,
SHOWING THAT AGAIN IT IS
ABSOLUTELY IMPORTANT.
SO ABOUT 4 IN 10 AFRICAN
AMERICANS ON DIALYSIS HAVE
KIDNEY FAILURE DUE TO THE APOL1
VARIANT.
AND IT'S ALSO HAS IMPLICATION IN
TERMS OF SURVIVAL AFTER KIDNEY
TRANSPLANTATIONS, HERE, SO
ALREADY HAVING SOME CLINICAL IMP
IICATIONS AND THIS IS CRITICALLY
IMPORTANT IN WEST AFRICA AND
SOME PARTS OF EAST AFRICA.
SO AGAIN, DUE TO ADMIXTURE THESE
VARIANTS HAVE NOW SPREAD ALL
OVER THE WORLD, SO THERE'S NO
REALLY WAY CAN YOU USE THE COLOR
OF PHENOTYPIC APPEARANCE TO
DETERMINE WHO WE HAVE THESE
VARIANTS, AGAIN REALLY IMPORTANT
THAT WE DO NOT MAKE ASSUMPTIONS
AND THE FACT THAT IS A RESULT OF
AFRICAN KIDNEY SICKNESS IS NOT
THE SUMMIT OF BEING AFRICAN
BECAUSE THERE ARE PARTS OF
AFRICA BECAUSE THEY DID NOT HAVE
OR DID NOT HAVE SUFFER THE
CONQUENCES OF THESE INFECTIONS,
AGAIN, IMPORTANT POINTS SO, 1 OF
THE POINTS, I WANT TO TRY TO
MAKE TO SUMMARIZE THE POINTS OF
ANCESTRY AND NOT USE PHENOTYPIC
APPEARANCE EIN TERMS OF CLINICAL
CARE, IS THIS IN CASE REPORT
THAT WAS PUBLISHED IN MEDICINE
1996, WE SHOWED THAT THE RACE OR
PHENOFINAL IPO PRICIC APIERANCE
CAN INDEED BE VERY DANGEROUS AS
WE MOVE TOWARDS PRECISION
MEDICINE AND THE PRACTICE OF
MEDICINE.
SO THIS IS A SERIOUS NEGATIVE
CONSEQUENCES OF PHYSICIAN'S
ASSUMPTIONS ABOUT A PATIENT'S
RACE.
AN 8 YEAR-OLD BOY
PHENOTYPEICALLY EUROPEAN PRESENT
WIDE ACUTE ABDOMINAL PAIN AND
ANEMIA, WITH A HEMATOCRIT OF
.21, TERM WAS ONLY 100-DEGREES
FAHRENHEIT, SURMINGRY WAS
CONSIDERED UNTIL A TECHNICIAN
RECOGNIZED THE HEMOLYTIC
CHARACTERISTICS ON A SMEAR.
SURGERY WAS CANCELED AFTER
RESULTS OF A SUBSEQUENT SICKLE
PREPARATION WERE FOUND TO BE
POSITIVE AND THE CHILD WAS
TREATED FOR UNDIAGNOSED SICKLE
CELL ANEMIA, NOW IT WOULD HAVE
BEEN PRETTY OBVIOUS, WHERE THIS
BAR GRAPH CAME FROM, EXPERIENCE
FROM GRENADDA AND INDIAN, NO 1
EUROPEAN AND MEDITERRANEAN
ANCESTRY AS YOU WILL RECALL OF
DISTRIBUTIONS SICKLE CELL USE IN
THESE PARTS OF THE WORLD INDEED
DO REFLECT THE ANCESTRAL
BACKGROUND.
SO, SO OVERALL THE POINT HERE IS
THAT INDIVIDUAL ANCESTRY IS MORE
IMPORTANT IN CONCEPT LIKE
AFRICAN HISPANIC OR ASIANS,
EUROPEANS AS WE MOVE TOWARDS HOW
WE DO PRECISION MEDICINE WE NEED
TO BE VERY, VERY KRSHES AND
RECOGNIZE THIS THAT YOU CAN USE
1 PERSON TO REPRESENT A GROUP.
AND THE DIVERSITY OF THE WORK
THAT WE DO ACROSS THE GLOBE, IS
REALLY UNEVEN AND WE PUSH TO
ESTABLISH THE HUMANITARIAN
EFFORT IN AMERICA, AND THE POINT
I WANT TO MAKE FOR THIS
CONSORTIUM AND MAKE ITS SO
WONDERFUL, IS THAT BY SEQUENCING
AFRICAN POPULATIONS AND FOCUSING
ON AFRICAN POPULATIONS THAT WE
ARE ABLE TO INFORM WHAT IS
HAPPENING AROUND THE WEST OF THE
WORLD.
SO IN ADDITION TO UNDERSTANDING
STRONG SELECTIONS IN TERMS OF
BACTERIA PROTECTION DEFENSE
AGAINST NEMATODES AND OTHER
TRAITS, WE WILL BE ABLE TO WORK
ON PATHOGENIC VARIANTS AND
BECAUSE THESE VARIANTS IN EUROPE
OR NORTH AMERICA, ARE COMMONLY
OBSERVED IN AFRICANS, SO
BRINGING INTO QUESTION WHETHER
IT'S TRULY PATHOGENIC, ALL WE
NEED TO UNDERSTAND THE GENETIC
BLACK GROUND IN WHICH VARIANT
MAY BE OPERATING AND AGAIN
UNDERSTANDING HISTORY I KNOW I'M
GOING OUT OF TIME A BIT SO I
WANT TO PUSH FORWARD.
SO I HOPE I HAVE CONVINCED YOU
BUT TO SOME EXTENT THAT
INCREASING DIVERSITY AND
UNDERSTANDING ANCESTRAL
BACKGROUND OF INDIVIDUALS IS A
SCIENTIFIC IMPERATIVE AND IF WE
DON'T DO IT IT'S A MISSED
OPPORTUNITY TO UNDERSTAND HUMAN
HISTORY AND HEALTH.
BUT THE OTHER POINT I WANT TO
MAKE IS THAT BETTER BEDDING OUR
ANCESTRY AND GENOMICS AND
BIOMEDICAL RESEARCH IN GENERAL
IS ALSO A SOCIAL JUSTICE ISSUE
IN THE SENSE OF WILL TOMORROW'S
MEDICINE WORK FOR ALL HUMAN
POPULATIONS OR ARE WE GOING TO
MISDIAGNOSE INDIVIDUALS BECAUSE
THE REFERENCE THAT THEY ARE
USING DO NOT SUFFICIENTLY
REPRESENT THE VARIATIONS THAT
EXIST IN THESE DIFFERENT GROUPS.
SO 1 WAY I WANT TO DEMONSTRATE
IN TERMS OF COMPLEX DISEASES IS
THE CONCEPT OF PATHOGENIC RISK
SCORES WHICH REALLY SAYS, BY
LOOKING AT THE VARIATIONS, AND
THE VARIANTS THAT WE HAVE
IDENTIFIED USING GWAS OR
DIFFERENT TRAITS, IF WE BRING
ALL OF THEM TOGETHER, WE CAN USE
IT TO STRATIFY INDIVIDUALS BY
RISK SO FOR EXAMPLE, INDIVIDUALS
AT THIS END WOULD BE CONSIDERED
HIGH RISK OR LOW RISK WILL
PROBABLY BE IN THE MIDDLE BUT
WHAT IS IMPORTANT HERE IS WHERE
WE DEVELOP THE STATISTICS, IS
HEAVILY INFLUENCED BY THE
DISCOVERY CIRCLES, SO IF FOR
EXAMPLE, THE DISCOVERY SAMPLES
IS MORE EUROPEAN, YOU SEE THAT
DWHEN WE TAKE THATA SET AND
USE IT TO TRAIN TO ELECTRIC AT
OTHER HEMO POPULATIONS WHAT
HAPPENS IS THAT AS THE DISTANCE
IN TERMS OF ANCESTRY, MOVED AWAY
FROM THE EUROPE, YOU SEE THE
ABILITY TO PREDICT INDIVIDUAL
RISK, REDUCES DRAMATICALLY AND
THEREFORE BEGIN EMPHASIZING THE
REASON WHY WE HAVE TO BE AGAIN,
TAKE ANCESTRY INTO CONCENTRATION
IN THE WORK THAT WE DO AND I'M
JUST GOING TO GO PAST THIS,
COMMITMENT POINT THAT GENETIC
VARIATION IS NORMAL FOR OUR
GENOME AND OUR DIVERSE IS NOT AN
ILLUSION, WE NEED TO STUDY THIS,
WE NEED TO DO THIS WITHOUT
FAMILY, PREJUDICE, NOTIONS OF
RACE, BECAUSE THE GENETIC
DIFFERENCES WE SEE BETWEEN US DO
NOT RISE TO THE LEVEL OF
[INDISCERNIBLE] OR UNIQUELY
DEFINE HEMO RACIAL GROUPS, SO
THE WHY WE ACTUALLY OR SERIOUSLY
TALK ABOUT THIS IN THE CONCEPT
OF RACE IS THAT TRYING TO USE
GENETICS TO DEFINE RACIAL GROUPS
IS LIKE SLICING SOUP.
YOU CAN CUT WHEREVER YOU WANT
BUT THE SOUP STAYS MIXED.
I HOPE I DEMONSTRATED THAT THAT
WE'RE ALL ARE MIXED WE JUST HAVE
DIFFERENT PROPORTIONS FROM
DIFFERENT PARTS OF THE WORLD.
SO IN THIS CONTEXT, WE ARE 1
HUMANITY BUT MANY, MANY, MANY
GENOMES AND WE NEED TO STUDY.
SO WE NOW HAVE THE TOOLS TO
REPRESENT OUR DIVERSITY THERE,
YOU KNOW PRESENT ALL AROUND THE
WORLD IS WE ARE BEGINNING TO
FUND RESEARCH THAT WILL HELP US
TO DEVELOP BETTER REFERENCES, SO
THAT WE CAN BETTER UNDERSTAND
HUMAN DISEASES, AND GENETIC
VARIATIONS ACROSS THE WORLD FOR
INSTANCE OF THESE YOU HUMAN
DISEASES AND JUST EMPHASIZING
THE WORK FROM 1 OF OUR
COLLEAGUES AT THE
[INDISCERNIBLE] AND OTHERS WHO
HAVE DONE FANTASTIC WORK IN
HELPING US TO COMLITE THE
SEQUENCE OF THE HUMAN GENOME AS
YOU MAY REMEMBER, WHEN THE HUMAN
GENOME IS PUBLISH INDEED 2003 OR
SO, THERE WAS STILL ABOUT AN 8%
GAP, BUT WE HAVE THE TECHNOLOGY
TO DO HA AND THERE IS THE P A
NGENOME IS NOW SET TO DEVELOP A
MORE REFERENCES GENOME THAT WE
POISED TO DO PRECISION MEDICINE
IN THE WAY THAT WILL BE
EQUITABLE AND TO THE REST OF THE
WORLD.
AS GENETIC EPIDEMIOLOGYS I WOULD
BE REMISS NOT TO TALK ABOUT THE
CONCEPT OF ENVIRONMENT,
SPECIFICALLY GENE ENVIRONMENT
INTERACTIONS AND THE POINT I
WANT TO MAKE SURE HERE IS THAT
FOR THE WORK THAT WE DO, IN THE
CENTER IN MY LAB AND THE
[INDISCERNIBLE], ESPECIALLY FOR
[INDISCERNIBLE] DISFARRITY, WHEN
WE TALK ABOUT [INDISCERNIBLE]
DISPARITY, MAY NOT BE DUE TO OUR
GENETIC PACK GROUND BUT MAY BE
DUE TO EXPOSURE IN THE
ENVIRONMENT.
IN THIS PARTICULAR CARTOON HERE,
THE POINT I WANT TO MAKE HERE IS
WHEN YOU LOOK AT THIS IS CHICAGO
AREA, WHEN YOU LOOK AT THE LOOP,
AGAIN, THIS AFFLUENT DOWN TOWN
NEIGHBORHOOD COMPARED TO
[INDISCERNIBLE], YOU SEE A HUGE
DIFFERENCE IN DISPARITY, THERE'S
INDIVIDUAL WHO IS MAY BE AFRICAN
AMERICANS IN BOTH GROUPS BUT
WHAT IS REALLY, REALLY FOR ME
OUTSTANDING IS WHEN YOU LOOK AT
HYDE PARK, WE LOOK AT A MIXTURE
OF AMERICAN AND NONAFRICAN
AMERICANS, AND WASHINGTON PARK
PREDOMINANTLY AFRICAN AMERICANS,
IT'S A HUGE DIFFERENCE, IT'S
WHAT THEY CALL A FOOTBALL FIELD
BETWEEN EACH OF THEM BUT YOU SEE
THE RADICAL DIFFERENCE IN THE
TERMS OF LIFE EXPECTANCY THIS,
IS NOT GENETICS THIS IS SOCIAL
STRUCTURE.
SO IN EMERGING ITS OF DISPARITY,
I THINK WE NEED TO BE AWARE THAT
GENETICS MAY BE IMPORTANT LIKE I
SHOWED IN TERMS OF KIDNEY
DISEASE, BUT MORE IMPORTANTLY
THE ENVIRONMENT AND THE WAY WE
SET UP OUR SOCIETY IS WHAT DRIVE
PEOPLE TO EXPLORE HEALTH IN THE
CONTEXT OF HEALTH DISPARITY AND
IT IS SOMETHING THAT WE CAN
REVERSE IF WE PAY ATTENTION TO
IT.
AND I WOULD LIKE TO STAND BY
THIS QUOTE THAT SAYS, IF THE
MYSTERY OF OUR CORE, BECAUSE
NOBODY LOVES NATURE BUT BY
INSTITUTIONS [INDISCERNIBLE]
CHARLES DARWIN OR WHAT SOME
PEOPLE MAY CALL THE FATHER OF
MODERN DAY GENETICS.
SO I WANT TO THANK YOU AND I
HOPE I HAVE CONVINCED YOU THAT
ANCESTRY IS REALLY IMPORTANT IN
TERMS OF GENETICS, DENATIONAL
LIBRARY OF MEDICINICS,
BIOMEDICAL RESEARCH AND
ESPECIALLY AS WE BEGIN TO THINK
ABOUT HOW WE CAN DEPLOY
PRECISION MEDICINE, YOU KNOW OR
DENATIONAL LIBRARY OF MEDICINIC
MEDICINE GLOBALLY AND
NATIONALLY, SO THANK YOU.
>> OKAY, LDR. ROTIMI, HAVE TO
THANK YOU SO VERY MUCH FOR AN
EXTREMELY BROAD REACHING AND
HIGHLY IMPACTFUL TALK I REALLY
TRULY ENJOYED IT AND YOU MAKE A
FANTASTIC CASE FOR MOVING PAST
SOCIAL CONSTRUCTS OF SKIN COLOR
AND RACE AND AND THE MORE
IMPORTANCE OF GENETIC AND
SIMILARITIES IN ANCESTRY AS IT
RELATES TO INFORMING MEDICAL
CARE AND DECISIONS AND YOU ALSO
WITH GREAT WISDOM PUT THE
CONTEXT OF YOUR RESEARCH INTO
THE IMPORTANCE OF ENVIRONMENTAL
FACTORS WITH YOUR LAST POINTS
THAT ALSO MEANINGFULLY AND
PREDOMINANTLY AFFECT WELL BEING,
WHAT A FANTASTIC TALK.
WE DO HAVE A KOWP QUESTIONS SO
AS THE MODERATOR I WILL TAKE THE
ADVABTAGE OF ASKING THE FIRST
QUESTION AND MY QUESTION FOR YOU
DR. ROTIMI IS--WHAT DO YOU SEE
AS THE MOST SIGNIFICANT
OBSTACLE, AS FURTHER ADVANCING
THIS TYPE OF RESEARCH AND BY
THAT I MEAN, GWAS BASED STUDIES
THAT FIND ASSOCIATIONS BETWEEN
GENES AND SPECIFIC ALLELIC
DIFFERENCES AND DISEASE STATES
AND THEN, TAKING THOSE
OBSERVATIONS AND THEN
IDENTIFYING OR SEEKING CAUSALITY
THROUGH TRANSLATIONAL MEDICINE
WHICH VERY ELEGANTLY SHOWED YOUR
EXAMPLES, WHAT DO YOU SLEEP
APNEA AND OBESITY AS THE BIGGEST
BARRIERS OFY VENTING THIS TYPE
OF RESEARCH FROM THOSE SUCH THAT
THOSE ALLEGATIONS AND CAUSALITY
GET TO FROM THE BEDSIDE.
>> YES, FIRST OF ALL THERE ARE
MULTIPLE LEVELS, WE NEED TO FUND
MORE DIVERSE COHORTS SO WE CAN
IDENTIFY MORE OF THESE TYPE OF
VARIANTS AND REALLY UNDERSTAND
THIS HUMAN HAPLOTYPE GLOBALLY SO
WE FLEED TO PROVIDE FUNDING TO
DO THIS DIFFERENTLY THAN WE
POSSIBLY WOULD BUT ONCE WE FIND
THESE VARIANTS, I THINK WE HAVE
A REAL BOTTLENECK IN TERMS OF
TRANSLATING OR UNDERSTANDING
WHAT THIS VARIANT WILL DO, I
THINK SOME OF IT THAT WE NEED TO
PUT IN PLACE IS WHAT I CALL
GENOME SCALE LEVEL TYPE OF
INTERROGATION OF THESE VARIANTS,
YOU KNOW IN A WAY THAT WE CAN
BEGIN TO UNDERSTAND THE BIOLOGY,
DEVELOPING MOTOR ORGANISMS CAN
HELP US TO UNDERSTAND SOME OF
THESE FUNCTIONS, LIKE WE
[INDISCERNIBLE] TYPE 2 DIABETES,
SO THERE NEEDS TO BE A RENEWED
EFFORT AND YOU KNOW ADDITIONAL
FUNDING AND THE ADDITIONAL
FUNCTIONAL INTERROGATION OF
VARIANTS THAT WE SEE AND THEN TO
HAVE AND TO LINK SOME OF THIS
VARIATION TO MEDICAL RECORDS SO
THAT WE CAN YOU KNOW DEVELOP A
PROCESS THAT SAYS MAKE WE CAN
STRATIFY INDIVIDUALS AND BE ABLE
TO KNOW HOW THESE VARIANTS MAY
BE IMPACTING THEIR HEALTH.
SO AGAIN TRYING TO LINK GENOMIC
VARIATIONS TO CLINICAL CONTEXT
IS REALLY IMPORTANT AND IS A
VERY DIFFICULT PROCESS, WE ARE
BEGINNING TO FUND STUDIES THAT
HELPING US TO DEMONSTRATE HOW WE
CAN LINK THIS KIND OF STUDIES
WITHIN THE CONCEPT OF CLINICAL
RECORDS TO FILL THIS GAP.
THE CLINICAL CENTER FOR EXAMPLE,
IS IDEAL FOR STUDYING THESE
TYPES OF EFFECTS SO WHEN IF WE
STUDY THREEZ, WE CAN COME TO THE
NIH CENTER, BRING IN INDIVIDUALS
IF ARE THIS AND PROPERLY
CHARACTERIZE THEM AND SEE AND
BEGIN TO BED WHAT THE VARIANTS
DO, YES.
>> THANK YOU FOR YOUR RESPONSE
DR. ROTIMI, LET ME SLIP IN 1
LAST QUESTION HERE THAT ASKS
ABOUT GENDER DIFFERENCES.
HAVE YOU LOOKED AT GENDER
DIFFERENCES IN YOUR COHORTS
EITHER FROM AFRICAN ANCESTRY OR
OTHERWISE WHERE YOU'VE
IDENTIFIED DIFFERENCES IN DEC
RISK FOR MEN VERSUS WOMEN.
SO WE TALK ABOUT GENDER IS
ANOTHER IMPORTANT FEATURE HERE.
>> YES, WE HAVE AGAIN, 1 OF THE
THINGS WE DO SEE VERY CLEARLY IS
GENDER DIFFERENCES FOR EXAMPLE
IN TERMS OF WEIGHT AND OBESITY.
SOME OF THAT IS TRULY BIOLOGICAL
BECAUSE I THINK VERY A VERY,
VERY LONG TIME WE'VE KNOWN THAT
THERE IS SEXUAL DISCIPLINARY
MORPHISM WHEN IT COMES TO HOW WE
STORE FAT.
SO FOR EXAMPLE, WE HAVE THIS
TYPICAL DESCRIPTION OF MEN
LOOKING APPLE OR WOMEN LOOKING
LIKE PAIRS AND THINGS LOAMACYIC
THAT SO THAT'S JUST AGAIN THE
MORPHISM IN HOW WE STORE FAT AND
THINGS LIKE THAT BUT WE DO SEE
DIFFERENCES, WHEN WE LOOK AT
PHENOTYPES LIKE THAT, BUT
OVERALL WE SEE THESE THINGS, WE
SLEEP APNEA AND OBESITY IT IN
DIFFERENT GROUPS MAYBE IN
DIFFERENT RATES, YOU KNOW SO
WITH THE KIND OF RESEARCH I DO,
WE HAVE NOT REALLY SEEN MAJOR
DIFFERENCES IN TERMS OF YOU KNOW
GENDER, YOU KNOW, SO, IT DOESN'T
MEAN THAT IT CAN EFFECT CANCER
AND HUGE DIFFERENCES DIFFERENT
TYPES OF CANCER, YOU KNOW, THAT
WE SEE AROUND THE WORLD.
SO BUT WHEN WE LOOK AT THINGS
LIKE DIABETES, HYPERTENSION, HOW
THOSE KIND OF CONDITIONS, THEY
ARE EQUAL OFFENDERS WHEN IT
COMES TO GENDER, YEAH.
>> DR. ROTIMI, AGAIN, WE'RE OUT
OF TIME AND I WILL FORWARD YOU
ADDITIONAL QUESTIONS FROM THE
AUDIENCE BUT WE WANT TO THANK
YOU SOPHISTICATEDY GREATLY FOR
YOUR EXCELLENT LECTURE TONIGHT
AND FOR YOUR THOUGHTFUL
RESPONSES TO THESE QUESTIONS.
THANK YOU AGAIN, DR. ROTIMI.
THANK YOU VERY MUCH.
AND THANKS TO EVERYBODY.