Human Heredity, the Human Heredity, the Environment and Environment and

Disease: Nature Disease: Nature andand NurtureNurture

National Human Genome Research

Institute

National Institutes of

Health

U.S. Department of Health and

Human Services

Emily L. Harris, Ph.D., M.P.H.Epidemiologist, Office of Population GenomicsNational Human Genome Research Institute

May 1, 2007

Nature and Nurture:Nature and Nurture:

Causal models & inferences from studying populations

Genes (or nature)

Environment (or nurture)

A Continuum of Causation

AND

Height

Nature and Nurture:Nature and Nurture:

Causal models & inferences fromstudying populations

Question: What causes the differences in height among individuals?

AND

Height

AND

Nutrition (environment)

Height

AND

Height

AND

Genes

Height

AND

Height

AND

Height

Genes & Environment

Nature and Nurture:Nature and Nurture:

Causal models & inferences fromstudying populations

Question: What causes the differences in height among individuals?

Conclusion: Depends on the population(s) studied.

Nature and Nurture:Nature and Nurture:

Multifactorial models incomplex diseases

Example: Cancer

a

R

Most Cancer Is NOT Inherited

Known Inherited Factor

All Breast Cancer Patients

Unknown Factor(s)

a

R

Chemical Bases in DNA

DNA molecule (chromosome)

Chemical bases

Gene

AT

CG

a

R

Altered DNA->Altered Protein

NucleusDNA

Protein

Chain of amino acids

Ribosome

Gene

DNA bases mRNA

Cell membrane

a

R

Many Mutations Lead to Cancer

Malignant Cells

NormalCell

FirstMutation

SecondMutation

ThirdMutation

Fourth orLater

Mutation

a

R

Most Cancer Is NOT Inherited

Known Inherited Factor

All Breast Cancer Patients

Unknown Factor(s)

Factors affectingFactors affectingCancer Development & Cancer Development &

ProgressionProgression Oncogenes (cancer promoting)Oncogenes (cancer promoting) Tumor suppressor genesTumor suppressor genes Carcinogen metabolism genesCarcinogen metabolism genes Immune surveillance for abnormal Immune surveillance for abnormal

cellscells

Some Factors affectingSome Factors affectingCancer Development & Cancer Development &

ProgressionProgression Oncogenes (cancer promoting)Oncogenes (cancer promoting) Tumor suppressor genesTumor suppressor genes

E.g., DNA repair proficiencyE.g., DNA repair proficiency Carcinogen metabolism genesCarcinogen metabolism genes Immune surveillance for abnormal Immune surveillance for abnormal

cellscells

DNA Repair & Cell PathologyDNA Repair & Cell Pathology

Author: Harold Brenner

Lifespan-influencing GenesLifespan-influencing Genes& DNA Repair& DNA Repair

Author: Harold Brenner

Genes (or nature)

Environment (or nurture)

A Continuum of Causation