genetics 101: demysifying genetics

“Genetics 101” Demystifying Genetics 

Kathleen Calzone, PhD, RN, APNG, FAANNational Cancer Institute, Center for Cancer Research, Genetics Branch

DNA Book

What is a Gene?Physical unit of inheritanceAre passed from parents to offspringContain information needed to specify traits

Genes are arranged on structures called chromosomes

Chromosomes contain a single long DNA molecule of which only a portion corresponds to a single gene

Humans have approximately 20,000 genes

Autosomal Dominant Inheritance

Each child has 50% chance of inheriting the mutation

No “skipped generations”

Equally transmitted by men and women

https://ghr.nlm.nih.gov/handbook/illustrations/patterns?show=autodominant

Autosomal Recessive Inheritance

Two germline mutations (one from each parent) to develop disease

Equally transmitted by men and women

https://ghr.nlm.nih.gov/handbook/illustrations/autorecessive

X-Linked

Mutant genes are on the X (sex) chromosome Women inherit 2 mutated copies to be affected Men who inherit the mutation are affected (only one X

chromosome)https://ghr.nlm.nih.gov/handbook/illustrations/xlinkrecessive

Definitions

Genetics – study of individual genes and their impact on relatively rare single gene disorders

Genomics – study of all the genes in the human genome together, including their interactions with each other, the environment, and other psychosocial and cultural factors

Cancer Arises From Loss of Normal Growth Control

Cancer cell division

Fourth orlater variantn

Third variant

Second variant

First variant

Uncontrolled growth

Cell Suicide or Apoptosis

Cell damage—no repair

Normal cell division

Germline (Inherited)/Somatic (Acquired)

EpigeneticsActivation and deactivation of genes without any change in the underlying DNA sequence of the organism

• Chemical compounds that modify genome function

• Are not part of the DNA itself

Preconception/Prenatal

Newborn Screening

Risk Identification

Screening/DiagnosisDisease

Characterization

IndividualizedTherapy

Management At End of Life

After EndOf Life

Genetic and Genomic Influences Across the Healthcare Continuum

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Calzone, et al. (2013). Relevance of genomics to healthcare and nursing practice. Journal of Nursing Scholarship. 45, 1-2.

Scope of Genomic InformationSources of genomic material

Blood, tumor, saliva, cheek swab •Stability of DNA•Testing can be performed on stored specimens

Family historyFeatures of a disease or disorder Family genetic test results

Obligate carrier

Obligate Carrier

http://www.genome.gov/27541954

• Begin colonoscopy at age 40

• Avoid high fat in diet

• Genetic defect targeted therapy for specific disease

• Drug dose of medication determined by drug metabolism genetic profile

Risk prediction Pharmacogenomics New Therapies

The Precision Medicine Initiative

DefinitionDisease treatment and prevention that incorporates individual genetic variation, environment and lifestyle

Overarching AimTo accelerate the pace of moving precision medicine into every day clinical practice.http://www.nih.gov/precisionmedicine/https://www.whitehouse.gov/precision-medicine

The Precision Medicine InitiativeExpand efforts in cancer genomics

Support trials testing combinations of targeted therapies based on tumor’s molecular signature

Develop solutions to drug resistance

Develop approaches assessing response to therapy

Develop new tumor cell models to predict response to drug combinations and define mechanisms of resistance

The Precision Medicine Initiative, cont

Long Term GoalsEstablish a research participant group of >1 million Americans who will share data, biologic samples, diet/lifestyle information, and linked to their Electronic Health Record if they choose.

Emphasis on engaged participants

Institute of Medicine Roundtable on Health Literacy

March 2, 2016-Health Literacy and Precision Medicine: An Important Partnership

Mission-inform, inspire, and activate a wide variety of stakeholders to support the development, implementation, and sharing of evidence-based health literacy practices and policies

http://iom.nationalacademies.org/Activities/PublicHealth/HealthLiteracy.aspx

Resources to Learn More

Talking Glossary http://www.genome.gov/Glossary

http://unlockinglifescode.org/

Next 3 Destinations: Unlocking Life's Code Exhibition Traveling ScheduleDiscovery World Milwaukee, Milwaukee, WI

January 18 - April 25, 2016Natural History Museum of Utah, Salt Lake City, Utah

May 21 - September 5, 2016Exploration Place, Wichita, KS

September 30 - January 1, 2017

Questions/Discussion

calzonek@mail.nih.gov301-435-0538