genetics

1. Genetics and Congenital Disorders
Pathology lecture 4
Dr Wesam Almagharbeh

2. outline
Pattern of Inheritance
Type of Congenital disorders: Genetic
Disorders, Malformations, Multifactorial
Disorders due to Environmental Influences:
Irradiations, Chemicals and Drugs,

3. Chromosome Review

4. Genetics
• Study of the patterns of inheritance
• Mendelian Genetics
– Gregor Mendel
– Pea plant experiments
• Grow easily
• Distinguishable characteristics
– Round/Wrinkly, Yellow/Green, Tall/Short
• Can control mating

5. Terminology
• Allele – Alternate forms of a gene
• Dominant Allele – trait that exerts its effects
whenever present
– Symbolized by capitol letter (B)
– Ex. Dwarfism, Huntington’s disease
• Recessive Allele – trait that is masked if a
dominant trait is present
– Symbolized by lower case letter (b)
– Ex. Blue eyes

6. Terminology
• Genotype – Genetic makeup of an organisms
– Homozygous – 2 alleles that are the same (BB or bb)
– Heterozygous – 2 different alleles (Bb)
• Phenotype – Observable characteristics
– Brown eyes, brown hair, tall, short
• Generation – group of organisms born around the
same time
– P Generation – Parental
– F1 – offspring of parent, first filial generation
– F2 – 1st generation of offspring

7. Genetic Terminology
Term Definition
Generations
P First (parental) generation
F1 children (Latin filii) of
generation P
F2 children of generation F1
Chromosomes and Genes
Chromosome macromolecules found in
cells, consisting of DNA,
protein and RNA
Gene unit of heredity of a living
organism
Locus specific location of a gene,
DNA sequence, or position on
a chromosome
Allele one of a number of
alternative forms of the same
gene or genetic locus
Term Definition
Dominant and recessive
Dominant Allele allele that is always expressed if present
Recessive Allele allele that is only expressed if the dominant
allele is not present
Genotypes and Phenotypes
Genotype genetic makeup of a cell, an organism, or an
individual
Homozygous contains two of the same allele of a gene
Heterozygous contains two different alleles of a gene
Phenotype organism's observable characteristics or traits
True Breeding pure-bred, is an organism that always passes
down a certain phenotypic trait to its offspring
Wild Type most common phenotype in nature
Mmutant physical or genetic difference from a mutation
in a gene

8. Tracking Inheritance
• Punnett Square – diagram showing genotypes
in a test cross
– Test cross – a Punnett square done to figure out
the genotype of an unknown
• Always use a homozygous recessive individual with
unknown
• Monohybrid Cross – Mating between
individuals that are BOTH heterozygous
• Dihybrid Cross – Mating between individuals
that are heterozygous for 2 traits (genes)

9. Genotypic ratio 1:2:1
(1 BB: 2 BB: 1 bb)
Phenotypic ratio 3:1
(3 pink: 1 white)
Monohybrid Cross

10. Dihybrid
Cross
Phenotypic ratio 9:3:3:1
(9 Smooth brown,
3 Smooth white
3 Curly brown
1 Curly white)

11. Laws of Segregation and
Independent Assortment
• Segregation - Two alleles of each gene are packed into
separate gametes
– Alleles move apart during meiosis
– Occurs during meiosis 1 – Metaphase
• Homologous chromosome move to opposite ends of
Poles
• Assortment - The segregation of alleles of one gene
does not influence the alleles for another gene
– Alleles are RANDOMLY packaged in gametes
– Use Product Rule – The chance that 2 independent events
will both occur = the product of individual chances that
each event will occur

12. Laws of Segregation and Assortment

13. Product Rule

14. Genetics Problem
The ability to curl your tongue up on the sides (T,
tongue rolling) is dominant to not being able to roll
your tongue. A woman who can roll her tongue
marries a man who cannot. Their first child has his
father’s phenotype. What are the genotypes of the
mother, father, and child? What is the probability
that their second child will be a tongue roller?

15. About 70% of Americans perceive a bitter taste from the
chemical phenylthiocarbamide (PTC). The ability to taste
this chemical results from a dominant allele (T) and not
being able to taste PTC is the result of having two
recessive alleles (t). Albinism is also a single locus trait
with normal pigment being dominant (A) and the lack of
pigment being recessive (a). A normally pigmented
woman who cannot taste PTC has a father who is an
albino taster. She marries a homozygous, normally
pigmented man who is a taster but who has a mother
that does not taste PTC. What percentage of the children
will be albinos? What percentage of the children will be
non-taster of PTC?
Genetics Problem

16. Recessive Disorders
• Recessive Disorder – disorder is ONLY expressed
when both alleles are recessive
– Can be “carried”
– Heterozygous individuals
can carry gene but not
express disease A a
A AA Aa
a Aa aa
Sickle Cell Anemia
Genotype Phenotype
AA Normal
Aa Carrier
aa Sickle Cell

17. Recessive Disorders
Sickle Cell Anemia

18. Dominant Disorders
• Dominant Disorder
– Condition is
expressed when an
individual has at least
one dominant allele
A a
A AA Aa
a Aa aa

19. Autosomal Disorders
Disorder Likelihood Major Symptoms
Recessive Disorders
Albinism 1/22,000 Lack of pigment in skin. appear white or very pale.
Skin can burn more easily from overexposure.
Cystic Fibrosis 1/2500
(Caucasions)
Excess mucus in lungs, digestive tracts, liver; increased susceptibility to infections,
death in early childhood if not treated
Galactosemia 1/60,000
(Caucasians)
Galactitol accumulates in body tissues. Results in an enlarged liver, cirrhosis, renal
failure, cataracts, brain damage, and ovarian failure. Mortality in infants is about 75%.
Phenylketonuria
(PKU)
1/15,000 (US) Abnormally high levels of phenylalanine accumulate in blood, toxic to the brain.
Intellectual disability, brain function abnormalities, mood disorders, irregular motor
functioning, and behavioral problems.
Sickle-cell disease 1/5,000 (US) May lead to tissue damage. Complications include risk of infection, stroke, and chronic
pain.
Tay–Sachs disease 1 /3,500
(Ashkenazi Jews)
Typically noticed in infants around 6 months, display abnormally strong response to
sudden noises or other stimulus, known as the “startle response.” There may also be
listlessness or muscle stiffness (hypertonia).
Dominant Disorders
Alzheimer’s disease unknown Dementia; memory loss, mental decay; not all cases are result of genetics
Huntington’s disease 5–10 /100,000 Neurodegenerative genetic disorder, affects muscle coordination, leads to cognitive
decline, behavioral symptoms.
Hypercholesterolemia unknown Presence of high levels of cholesterol in blood; can lead to atherosclerosis and other
heart problems; can be caused by genetics or lifestyle

20. Variations on Mendel’s Laws
• Pleiotropy
– One gene has many
effects
Sickle Cell
Allele
Abnormal
Protein
Abnormal
Shaped
Red Blood
Cell
Organ Damage
Kidney Failure
Heart Failure
Spleen Damage
Brain Damage
Other Effects
Pain and Fever
Joint Problems
Physical Weakness
Anemia
Pneumonia

21. Variations on Mendel’s Laws
• Polygenic Inheritance – Many genes control
one phenotype
– Eye color, hair color, height, skin color

22. Sex Linked Genes
• Sex Determination
– Female – XX
– Male – XY
• Can be carried on either
X or Y chromosome
– More common on X
chromosome
• Affect more males than
females

23. XA Xa
XA XAXA XAXa
Y XAY XaY

25. X-Linked Disorders
Disorder Genetics Characteristics
X-Linked Recessive Inheritance
Duchenne muscular dystrophy Mutation in dystrophin gene Early life muscle degeneration; eventual death
Fragile X syndrome Expansion of CGG trinucleotide
repeat on X chromosome
Most widespread single-gene cause of autism and
inherited cause of intellectual disability, especially
among boys
Hemophilia A Mutant allele; ~70% of the time X-
linked recessive trait, ~30% of cases
arise from mutations
Deficiency in clotting factor VIII, causes increased
bleeding; usually affects males
Red–green color blindness Absence or mutation of genes for
red or green color receptors
Difficulty discriminating red and green hues
Rett syndrome Mutations in gene MECP2 located
on X chromosome
Typically no verbal skills, 50% of individuals
affected do not walk. Scoliosis, growth failure,
constipation very common
X-Linked Dominant Inheritance
Hypertrichosis Unknown Abnormal amount of hair growth over body
X-linked hypophosphatemia Mutation in PHEX gene sequence
(Xp.22); subsequent inactivity of
PHEX protein
Can cause bone deformity including short stature
and genu varum (bow leggedness).
Retinitis pigmentosa (some
forms)
Unknown Degenerative eye disease; causes severe vision
impairment; often blindness