Genetics and Health

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Genetics and Health

• Miriam G. Blitzer, PhD
• Professor, Department of Pediatrics
• Head, Division of Human Genetics
• University of Maryland School of Medicine
• September 10, 2008

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What is the most important reason to think about
human genetics?
WE ARE!!! Your genes
can be compared to your own personal blueprint.
Our genes hold the secrets to who we are, where
were from and how were made.
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Overview GENETICS 101

• What are genes and DNA?
• What is Genomic Medicine and why is it important
  to our health?
• How do we inherit genetic disease?
• How can knowing our family history improve our
  health?

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DNA in Context
(Not to scale!)
The human body is made of millions of cells. Each
contains identical copies of all of our genetic
material.
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DNA in Context
(Not to scale!)
The human body is made of millions of cells. Each
contains identical copies of all of our genetic
material.
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DNA - deoxyribonucleic acid

• The molecule inside each cell that carries the
  genetic instructions for making living organisms
  Instruction Manual
• Double-stranded - made up of four building blocks
  called nucleotide bases A, T, C, G

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Human sperm contains 23 chromosomes numbers 1-22
plus either an X or a Y chromosome.
The union of sperm and egg creates a human embryo
with 46 complete chromosomes.
A human egg contains 23 chromosomes numbers 1-22
plus a single X chromosome.
m)
embryo
l)
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Whats a ____?

• Gene segment of DNA coding a compound,
  (responsible for every body function)
• Genome all of the DNA in an organism
• Size of human genome 3.4 billion base pairs
• Number of human genes 25,000
• Only about 5 of the human genome contains genes

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What is a Mutation??

• Change in the DNA -
• Substitution of one base (letter) for another
• Deletion or duplication of a piece of DNA
  sequence
• Insertion of new DNA material
• COULD LEAD TO DISEASE, MILD VARIATION or NO
  CLINICAL FINDINGS AT ALL
• MOST IMPORTANT leads to variation -gt make us
  individuals!

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Impact of Genetic Disease

• Estimated that 3-7 of the population will be
  diagnosed with a recognized genetic disorder, NOT
  INCLUDING common disorders, such as cancer,
  diabetes, heart disease, and psychiatric
  disorders
• 3 of newborns have a significant genetic
  disorder
• Genetic disorders account for 10 of pediatric
  admissions in the U.S.

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ALL DISEASE (WITH THE POSSIBLE EXCEPTION OF
TRAUMA) IS GENETIC!
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gt 9 of the CDCs 10 Leading Causes of U.S.
Deaths Have Genetic Components

• 1. Heart disease (31.0 of deaths in 98)
• 2. Cancer (23.2)
• 3. Stroke (6.8)
• 4. COPD (4.8)
• ? 5. Injury (4.2)
• 6. Pneumonia/Influenza (3.9)
• 7. Diabetes (2.8)
• 8. Suicide (1.3)
• 9. Kidney disease (1.1)
• 10. Chronic liver disease (1.1)

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Medical Genetics/Genomic Medicine

• Underlying basis for ALL conditions, including
  common/complex diseases asthma, hypertension,
  diabetes, psychiatric disorders
• Genomics study not just of single genes, but
  of the functions and interactions of all the
  genes in the genome

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Family History

• Reflects the consequences of genetic background,
  shared environment and common behaviors.
• Allows us to identify potentially inherited
  disorders in families.
• Is an independent risk factor for most chronic
  diseases of public health significance.

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PEDIGREE SYMBOLS
AFFECTED
DECEASED
2
AFFECTED
PROBAND
AFFECTED
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Male / boy
Female / girl
This line is used to show parents who are
divorced/not together
Adopted

• What if there is limited information
• about family members?
• If you do not know names and ages of
  familymembers, but do know the number of boys
  andthe number of girls, you can do this
• If you do not know the number of boysand the
  number of girls, use diamond with number inside
  it (if total is known) or ?.

The diagonal line is used to show that the
person has died.
Pregnancy loss. Include number of weeks, if
known.
Example This shows that there are 5 boys and 3
girls.
3
5
SB stands for stillbirth. Include number of
weeks, if known.
SB
8
Example This shows that there are 8 children.
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England and Germany
Mexico
Grandfather
Grandmother
Grandfather
Grandmother
60s Colon cancer
70s Breast cancer (diagnosed 68)
65 Heart attack
85
Pregnancy Loss 8 weeks
Father
Mother
Aunt
Uncle
Uncle Adopted
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49
47
62
High blood pressure
High cholesterol
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3
2
Twins Non-identical
First cousins
First cousin
Half-sister (same mother,different father)
30s-40s
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Sister
You
Brother
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22
24
18
Club foot
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Niece
Nephew
2
6 months
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Single Gene Traits/Conditions

• Those traits that are determined by a change in
  one particular gene
• Characterized by their transmission pattern in
  families
• Able to determine risks for specific family
  members if know how this is passed on in the
  family

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Autosomal Dominant Inheritance

• Vertical transmission (generation to generation)
• On average, 50 of offspring of affected parent
  will be affected
• Unaffected individuals do not pass on trait
• Males and females both affected

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Autosomal Dominant Conditions

• Marfan Syndrome
• Achondroplasia (common Dwarfism)
• Familial (early-onset) Alzheimer Disease
• Huntington Disease
• Familial Hypercholesterolemia
• Familial Breast Cancer (BRCA1 or BRCA2
  mutations)

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Autosomal Recessive Inheritance

X
Carrier female, UNAFFECTED
Carrier male, UNAFFECTED
AFFECTED CARRIER
CARRIER NON-CARRIER
NOT-AFFECTED
25 chance 50 chance
25 chance
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Autosomal Recessive Inheritance

• Trait typically seen in siblings but usually not
  in earlier generations (unaffected, carrier
  parents)
• On average, 25 recurrence risk
• Males and females equally affected
• Increased consanguinity (relatedness) seen
• Carriers of the mutant gene are normal but can
• pass the trait to offspring

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Autosomal Recessive Conditions

• Sickle Cell disease
• Cystic Fibrosis
• Tay-Sachs disease
• Phenylketonuria (PKU)
• Thalassemias

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X-linked Recessive Traits

• Duchenne muscular dystrophy
• Hemophilia A
• Color blindness

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Common Diseases With a Confirmed Genetic Component

• Hypertension
• Diabetes Mellitus I II
• Alzheimer Disease
• Cardiovascular disease
• Cancer
• Osteoporosis
• Psoriasis

• Glaucoma
• Age-related Hearing Loss
• Schizophrenia
• Bipolar Disease
• Depression

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Is Cancer Inherited?

• Most cancers are NOT inherited
• Not due to a predisposing factor that is passed
  down from parent to child
• 90-95 are sporadic
• No clear pattern in the family
• Later age of onset

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Sporadic Cancer
dx. 76
Breast
Ovarian
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Hereditary Cancer

• 5-10 of all cancers
• Multiple relatives affected
• Early onset
• Multiple cases of cancer in same relative
• Rare cancers

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Hereditary Cancer
dx. 42
dx. 55
dx. 44
dx. 76
Breast
Ovarian
dx. 38
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Red Flags

• Multiple cases of breast cancer in the same
  genetic lineage, particularly at a young age
• Presence of breast and ovarian cancer on the same
  side of the family
• Early age at diagnosis (particularly breast
  cancers)
• Male breast cancer
• Bilateral breast cancer

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What is a Genetic Counselor?

• Masters Level trained Health Professional
• Work with the patient and family to
• Understand the medical facts of the genetic
  condition
• Learn more about genetics and risk of recurrence
• Understand the available options
• Help make decisions about those options
• Provide emotional and psychosocial support

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Why focus on family history?

• FH is underutilized in preventive medicine
• geneticists use of pedigrees
• FH is risk factor for many common diseases
• current strategies not working (diet, exercise,
  smoking)

Jim Fixx 1932 - 1984
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Most important genetic evaluation (test)

• FAMILY HISTORY
• www.ashg.org
• www.hhs.gov/familyhistory/
• http//www.cdc.gov/genomics/public/famhistMain.htm
  
• http//geneticalliance.org

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Surgeon Generals American Family Health
Initiative

• Thanksgiving Family History Day
• every time you get together with your family,
  you should have a conversation to learn more
  about who among your family and blood relatives
  suffered from what kinds of illnesses - and then
  write it down with the new tool or just on a
  piece of paper so you will remember to tell it to
  your doctor. Youll be amazed at what you learn -
  and not just about disease.
• --Former U.S. Surgeon General Richard H. Carmona

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U.S. Surgeon Generals Family History
Initiative http//www.hhs.gov/familyhistory/ W
eb-based or paper copy
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The most powerful ties are to the ones who gave
us birth.no matter how many years have passed,
we remain connected. Anthony Brandt
a)
b)