Introduction to Human Genetics

Dr Hodan A. Ibrahim

09/08/21 21:35 Dr Hodan A. Ibrahim 1

 Genetics Course outline

 Introduction to genetics
 Chromosomes: The physical basis of Inheritance
 Mendelism: inheritance as probability
 Autosomal and Sex linked patterns of inheritance
 Chromosome Aberrations and Gene Mutations
 The Molecular Basis of Inheritanc

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 Ground rules of the
class

 Be punctual & keep attendance;
 All teaching materials to be in place in the class;
 No side talk in the class; if this happens will be out of
the class;
 You can raise questions properly;
 Class participation will be considered;

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 Impact of Genetic
Disease

Estimated that 3-7% of the general population will be
diagnosed with a recognized genetic disorder, NOT
INCLUDING common disorders, such as cancer,
diabetes, heart disease and psychiatric disorders
 ~3% of pregnancies are of a child with a significant
genetic disorder
 Genetic disorders account for 10% of pediatric
admissions in the U.S.

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Genetic variations cause inherited
diseases

Diseases with
Environmental Genetic Diseases heredity
Diseases
predisposition
- Infection - Cystic fibrosis
- Down syndrome - Cardiovascular
- Traumas Disease
- burns - Sickle cell disease
- DM type 2
- Phenilcetonuriae
-cancer

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- Environment
Dr Hodan A. Ibrahim - Genes 5
> 9 of the CDC’s 10 Leading Causes of Deaths Have
Genetic Components

 1. Heart disease (31.0% of deaths in )
 2. Cancer (23.2%)
 3. Stroke (6.8%)
 4. COPD (4.8%)
 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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 Classical and Modern
Genetics

 Humans have long understood that offspring tend to
resemble parents, and have selectively bred animals
and plants for many centuries.
 The principles of heredity were first explained by
Mendel in the mid nineteenth century, using defined
crosses of pea plants.

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 
 Recent important milestones in genetics include:
a. Berg’s construction (1972) of the first recombinant
DNA molecule in vitro.
b. Boyer and Cohen’s first cloning (1973) of a
recombinant DNA molecule.
c. Invention by Mullis (1986) of the polymerase chain
reaction (PCR) to amplify specific DNA sequences

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 Basic Genetics

 Genetics is the study of biologically inherited
traits determined by elements of heredity that
are transmitted from parents to offspring in
reproduction. These inherited elements are
called genes.
 Recent advances in the field of genomics have
led to development of methods that can
determine the complete deoxyribonucleic acid
(DNA) sequence of an organism.
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 
 Genomics is the latest advance in the study of the
chemical nature of genes and the ways that genes
function to affect certain traits.
 The work of Gregor Mendel, a monk and part-time
biologist, with garden peas is regarded as the
beginning of what would become the science of
genetics.

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 
Mendel is showed the existence of genes as
well as illuminating the rules governing their
transmission from generation to generation.
The study of genetics through the analysis of
offspring from mating is sometimes referred
to as classical genetics.

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 
The billions of nucleotides in the nucleus of a
cell are organized linearly along the DNA
double helix in functional units called genes.
Each of the 20,000 to 25,000 human genes is
accompanied by various regulatory elements
that control when that gene is active in
producing messenger ribonucleic acid
(mRNA) by the process of transcription.
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 
In most situations, mRNA is transported
from the nucleus to the cytoplasm, where its
genetic information is used in the
manufacture of proteins (a process called
translation)

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 Chromosomes
 are which the genes are

transmitted from
generation to generation.
 Each chromosome is a
complex of protein and
nucleic acid in which an
unbroken double helix of
DNA is tightly wound
 Genes are found along
the length of
chromosomes.
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 09/08/21 21:35 Dr Hodan A. Ibrahim 15
http://www.ncbi.nlm.nih.gov/
 
 humans normally have 46
chromosomes, which are
arranged in 23 pairs.
 One of these pairs,
consisting of the sex
chromosomes X and Y,
determines the sex of the
individual; females have
the pair XX and males
have the pair XY

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 
The exact location of a gene on a
chromosome is known as its locus,
Currently, researchers have identified the
chromosomal sites of more than 11,000 genes
(i.e., those for which normal or abnormal
function has been identified).

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 

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 Mutation
A mutation is defined
as a change in DNA
that may adversely
affect the host
The most dramatic
mutation is either
alter physical
structure or number
of chromosomes

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 Genes
Most human characteristics and common diseases
are


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 Single gene disorders

• Single mutant gene has a large effect
on the patient
• Transmitted in a Mendelian fashion
• Autosomal dominant, autosomal
recessive, X-linked, Y-linked
• Osteogenesis imperfecta - autosomal
dominant
• Sickle cell anaemia - autosomal recessive
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• Haemophilia - X-linked
 Polygenic diseases

• 
The most common still the least
understood of human genetic diseases

• Result from an interaction of multiple

genes, each with a minor effect

• The susceptibility alleles are common

• Type I and type II diabetes,

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autism, 22
osteoarthritis
 Chromosomal mutation

Effect entire chromosomes
 deletion
 duplication
 inversion
 translocation

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 Medical Genetics

Any application of genetic principles
to medical practice.
“Genetics – study of individual genes
and their effects”

Includes studies of inheritance, mapping

disease genes, diagnosis and treatment,
and genetic counseling.
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 DNA - deoxyribonucleic
acid

 The molecule inside each cell that carries the genetic
instructions for making living organisms.
 Double-stranded - made up of four building blocks
called nucleotide bases: A, T, C, G
 The human genome has 3 billion pairs of bases.

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 Human Chromosome
Facts

 Number of chromosomes per somatic cell: = 46
 Number of chromosomes per gamete (egg/sperm): 23
 One chromosome of each pair donated from each parent’s
egg or sperm
 Sex chromosomes: XY for males; XX for females
 Largest chromosome #1 = ~263 million base pairs (bp)
 Smallest chromosome Y = ~59 million bp

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 What’s

 Gene = The functional and physical unit of heredity
passed from parent to offspring

 Chromosome = Thread like structures on which the

genes reside and organized

 Locus = Position of a gene on a chromosome

 Mutation = A change in the DNA sequence

(permanent, heritable)

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 Family History

• Reflects the consequences of genetic susceptibilities,
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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 Male / boy
Female / girl
Adopted
The diagonal line
is used to show that
the person has died.
Pregnancy loss.
Include number
of weeks, if known.
SB stands
for stillbirth.
SB
Include number of
weeks, if known.
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This line is used to show
parents who are divorced/not together
What if there is limited information
about family members?
•If you do not know names and ages of family
members, but do know the number of boys and
the number of girls, you can do this:
Example: This shows that there
5 3
are 5 boys and 3 girls.
•If you do not know the number of boys
and the number of girls, use diamond
with number inside it (if total is known) or “?”.
Example: This shows that
8 there are 8 children.
29
 Single Gene
Traits/Disorders

 Those traits are determined by one particular gene
 Characterized by their transmission pattern in families
– PEDIGREE ANALYSIS
 Able to determine risks for particular family members
if know mode of inheritance

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 Common Genetic Terms

 Genotype: An individual’s genetic makeup - forms of a
particular gene at a given locus

 Phenotype: The observable expression of a genotype

 Homozygous: Identical forms of a particular gene

 Heterozygous: Different forms of a gene– CARRIER if one

normal and one abnormal

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 Common Genetic Terms

 Dominant: Condition phenotypically expressed in
someone carrying one copy of a mutant gene

 Recessive: Condition phenotypically expressed only in

someone with two copies of the mutant gene

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 AUTOSOMAL DOMINANT INHERITANCE

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 Autosomal Dominant
Inheritance

 Vertical transmission
 On average, 50% of offspring of affected parent will
be affected

 Unaffected individuals do not transmit trait

 Males and females equally affected

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 Autosomal Dominant
Conditions

 Marfan Syndrome
 Achondroplasia
 Familial (early-onset) Alzheimer Disease
 Huntington Disease
 Familial Hypercholesterolemia
 Familial Breast Cancer (BRCA1 or BRCA2
mutations)

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 Autosomal Recessive Inheritance

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 Autosomal Recessive
Inheritance

 Horizontal transmission; disease in siblings but usually
not in earlier generations (unaffected, carrier parents)

 On average, 25% recurrence risk

 Males and females equally affected

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 Autosomal Recessive
Conditions

 Sickle cell disease
 Cystic fibrosis
 Tay-Sachs disease
 Hemochromatosis
 Phenylketonuria
 Thalassemias

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 X-linked Recessive Inheritance

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 X-linked Recessive
Inheritance

Incidence of trait is much higher in males than
females
No father-to-son transmission
50% of sons of carrier mother are affected and
50% of daughters are carriers
Trait may be transmitted through series of
carrier females

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 X-linked Recessive
Disorders

 Duchenne muscular dystrophy
 Hemophilia A
 Color blindness
 Glucose-6-phosphate dehydrogenase (G6PD)
deficiency

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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
 95-90% 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. 61


dx. 55 dx. 44 dx. 76

Breast

dx. 38 Ovarian
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 

Thanks for your attention

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