INTRODUCTION

Genetic Disorder are medical conditions

caused by mutations of genes. Mutations is any
heritable change in the genetic make up of an
individual. In other words mutations are the
changes in the DNA sequence of the gene thus
causes genetic disorders.
 Medical Genetics

“ Medical genetics is the science of human

biological variation relates to health and diseases.”
- Victor A. McKusik
 Gene
• A functional unit that is regulated by
transcription and encodes a product, either a
protein or RNA
• There are about 30,000 genes in the human
genome (2% code for protein)
• Account for only about 10-20% of DNA
• A single gene can generate multiple spliced
mRNA products which are translated into
proteins and are subject to complex post
translational modification
 The genetic diseases fall into four categories:

• Diseases related to single gene mutations of large effect

(Mendelian disorders)

• Diseases related to multiple gene mutations of small effect

(Polygenic)

• Diseases arising in chromosomal aberrations (Cytogenetics

disorders) numeric or structural changes in chromosomes

• Non traditional inheritance (Mitochondrial Disorders)

• Genetic imprinting diseases 

 Single-Gene Disorders
• Single-gene disorders are diseases caused
by a mutation within one gene
• Autosomal dominant disorder: mutated
gene is an autosome that is dominant
• Autosomal recessive disorder: two copies of
a mutated gene on an autosome
• Sex-linked disorder: mutated gene is on the
sex chromosome
 Monogenic disorders
• Many are connected with inborn errors of
metabolism
• Some (preventable ) forms are subjects of neonatal
screening programs
– Phenylketonuria,
– Congenital hypothyreosis
– Sickle-cell anaemia
– Congenital adrenal hyperplasia
– Galactosaemia,
– Biotinidase deficiency
– Maple syrup urine disease
Sickle-cell disease (SCD), or sickle-cell anaemia (or
anemia; SCA) or drepanocytosis, is an autosomal co-
dominant genetic blood disorder characterized by red
blood cells that assume an abnormal, rigid, sickle shape.

Sickling decreases the cells' flexibility and results in a risk

of various complications. The sickling occurs because of a
mutation in the haemoglobin gene.

Life expectancy is shortened, with studies reporting an

average life expectancy of 42 in males and 48 in females.
Sickle-cell disease, usually presenting in childhood, occurs
more commonly in people (or their descendants) from parts
of tropical and subtropical regions where malaria is or was
common.

One-third of all indigenous inhabitants of sub saharan

Africa carry the gene, because in areas where malaria is
common, there is a fitness benefit in carrying only a single
sickle-cell gene.

Those with only one of the two alleles of the sickle-cell

disease, while not more resistant, are more tolerant of
infection and thus show less severe symptoms when
infected.
The prevalence of the disease in the United States is
approximately 1 in 5,000, mostly affecting Americans of
Sub-Saharan African descent, according to the National
Institute of Health.

In the United States, about 1 in 500 African-American

children born will have sickle-cell anaemia.
Sickle-cell anaemia is the name of a specific form of sickle-
cell disease in which there is homozygosity for the mutation
that causes HbS. Sickle-cell anaemia is also referred to as
"HbSS", "SS disease", "haemoglobin S" or permutations
thereof.
In heterozygous people, who have only one sickle gene and
one normal adult haemoglobin gene, it is referred to as
"HbAS" or "sickle cell trait".
Other, rarer forms of sickle-cell disease include sickle-
haemoglobin C disease (HbSC), sickle beta-plus-
thalassaemia (HbS/β+) and sickle beta-zero-thalassaemia
(HbS/β0). These other forms of sickle-cell disease are
compound heterozygous states in which the person has only
one copy of the mutation that causes HbS and one copy of
another abnormal haemoglobin allele.
The term "sickle cell crisis" is used to describe several
independent acute conditions occurring in patients with
sickle cell disease. Sickle cell disease results in anaemia and
crisis that could be of many types including
The vaso-occlusive crisis, aplastic crisis, sequestration crisis
, hyper haemolytic crisis and others. Most episodes of sickle
cell crises last between five and seven days.

The vaso-occlusive crisis is caused by sickle-shaped red

blood cells that obstruct capillaries and restrict blood flow to
an organ, resulting in ischaemia, pain, necrosis and often
organ damage.
Because of its narrow vessels and function in clearing defective
red blood cells, the splees is frequently affected. It is usually
infarcted before the end of childhood in individuals suffering
from sickle-cell anaemia. This autosplenectomy increases the
risk of infection from encapsulated organisms preventive
antibiotics and vaccinations are recommended for those with
such asplenia.

Aplastic crises are acute worsenings of the patient's baseline

anaemia, producing pallor, tachycardia, and fatigue. This crisis
is triggered by parvovirus B19, which directly affects
erythropoiesis (production of red blood cells) by invading the
red cell precursors and multiplying in them and destroying
them.
Haemolytic crises are acute accelerated drops in haemoglobin
level. The red blood cells break down at a faster rate. This is
particularly common in patients with co-existent G6PD
deficiency. Management is supportive, sometimes with blood
transfusions.
Sickle-cell anaemia is caused by a point mutation in the β-
globin chain of haemoglobin, causing the hydrophilic
amino acid glutamic acid to be replaced with the
hydrophobic amino acid valine at the sixth position. The β-
globin gene is found on the short arm of chromosome 11.

The association of two wild-type α-globin subunits with

two mutant β-globin subunits forms haemoglobin S (HbS).
Under low-oxygen conditions (being at high altitude, for
example), the absence of a polar amino acid at position six
of the β-globin chain promotes the non-covalent
polymerisation (aggregation) of haemoglobin, which
distorts red blood cells into a sickle shape and decreases
their elasticity.
 Sickle Cell Anemia
• Defective hemoglobin S molecule
• Symptoms:
Tiredness and sores on the legs
Swelling of hands and feet
Susceptibility to respiratory infections
• Recessive gene
• 50,000 patients in the United States
• Malaria protection
Sir Archibald Garrod
 The One Gene - One Enzyme Hypothesis:
Background
• Early in the 20th century, Sir Archibald Garrod studied a
number of inborn errors of metabolism:
– Garrod and his father were physicians and his brother was a
zoologist.
– Garrod’s father was interested in the chemical basis for arthritis
- the condition of alkaptonuria is associated with a type of arthritis.
– Individuals afflicted with alkaptonuria secrete homogentisic acid
(also called alkapton or 2,5-dihydrophenylacetic acid) in urine -
this compound turns black when urine stands.
– Homogentisic acid also accumulates in cartilaginous tissues,
leading to a darkening of the nose and ears.
– In addition to alkaptonuria, Garrod also studied disorders such as
albinism and cystinuria.
 History of Alkaptonuria
• Boedecker ‘alkapton’ 1859

• Wolkow & HGA 1891

Baumann

• Garrod ‘inherited disorder’ 1902

? Enzyme deficiency

• LaDu et al Homogentisic acid oxidase

deficiency proved 1958

• Pollak et al AKU gene on 3q2 1993

 •Alkaptonuria (black urine disease or alcaptonuria) is a
rare inherited genetic disorder of phenylalanine and
tyrosine metabolism.
•This is due to a defect in the enzyme homogentisate 1,2-
dioxygenase, which participates in the degradation of
tyrosine.
As a result, a toxic tyrosine byproduct called
homogentisic acid (or alkapton) accumulates in the blood
and is excreted in urine in large amounts(hence -uria).
Excessive homogentisic acid causes damage to cartilage
(ochronosis, leading to osteoarthritis) and heart valves as
well as precipitating as kidney stones.
 Clinical Features of AKU
• Dark urine
• Ochronosis
• Arthritis

• Musculoskeletal (muscle and ligament tears)

• Cardiovascular (valvulitis, fibrosis, calcification)
• Genitourinary (renal and prostatic calculi, renal failure)
• Hearing loss
 Alkaptonuria - Clinical Manifestations
• The pigmentation phenotype is called ochronosis.
– Note the pigmentation of the ear and eyes.

• The arthritis is associated with calcification of joints.

– All of these images are of a
67-year old patient.
– Note the posture and
spinal x-ray.
– She was treated with a hip
replacement - her bones
were damaged & stained.
Alcaptonuria
 Alkaptonuria - Biochemistry
• Alkaptonuria reflects the absence of homogentisic acid
oxidase activity.
 Alkaptonuria - Genetics
• Alkaptonuria is now known to reflect the absence of
homogentisic acid oxidase activity.
– Garrod found that alkaptonuria is inherited as a single gene
recessive trait.
– He hypothesized that a gene was necessary for homogentisic
acid oxidase activity, and that there was a recessive allele of this
gene could not produce a functional enzyme to catalyze this
reaction.
– Garrod also studied the alkaptonuria phenotype by increasing
dietary protein (remember, Phenylalanine is an amino acid).

– WHAT WOULD YOU EXPECT IF YOU INCREASED PROTEIN

INTAKE FOR AN INDIVIDUAL WITH ALKAPTONURIA?
 Alkaptonuria - Genetics
• Alkaptonuria is now known to reflect the absence of
homogentisic acid oxidase activity.
– Garrod found that alkaptonuria is inherited as a single gene
recessive trait.
– He hypothesized that a gene was necessary for homogentisic acid
oxidase activity, and that there was a recessive allele of this gene
could not produce a functional enzyme to catalyze this reaction.
– Garrod also studied the alkaptonuria phenotype by increasing
dietary protein (remember, Phenylalanine is an amino acid).

– He observed increased homogentisic acid secretion in affected

individuals but not in normal individuals.
• Since these individuals are receiving more protein, they have
more Phenylalanine to metabolize, so they make and excrete
more homogentisic acid.
 Mucopolysaccharidoses

•Mucopolysaccharidoses are a group of metabolic disorders

caused by the absence or malfunctioning of lysosomal enzymes
to break down molecules called glycosaminoglycans - long
chains of sugar carbohydrates in each of our cells that help build
bone, cartilage, tendons, corneas, skin and connective tissue.

• Glycosaminoglycans are also found in the fluid that lubricates

our joints.

•The result is permanent, progressive cellular damage which

affects appearance, physical abilities, organ and system
functioning, and, in most cases, mental development.
 Alkaptonuria ENZYME PROPERTIES
Inborn error of metabolism
• 448 AA polypeptide
Autosomal recessive
• MW 50,168

• 21 histidine and 23 tyrosine residues

Homogentisate • Functional hexamer arranged as

1,2 dioxygenase
dimers of 3

AKU GENE
Located on Chromosome 3(q2)

60Kb long and 14 exons

Common mutations (P230S, V360G,

M368V)
 ENZYME ACTIVITY IN AKU
Mutations lead to inactive HGD
Enzyme activity Tyrosine
umol/h/g liver g/day

metabolised

Normal 270 1600

AKU <0.05 -
Heterozygote 140 800

Homogentisate
1,2 dioxygenase

PLASMA HGA LEVELS IN AKU

Plasma HGA Urine HGA
Normal 6ug/l -
AKU 6mg/l 6g/24h
 Metabolic Pathway of Ochronotic Pigment Production

DIETARY PROTEIN
100g of protein = 4g of Phenylalanine/3g of Tyrosine
MALEYLACETOACETATE
TYROSINE
Homogentisic acid 1,2 dioxygenase (HGD) deficiency
BLOCK IN ALKAPTONURIA

2 (0)
POLYMER
(0)
HOMOGENTISIC ACID HGA
BENZOQUINONE HGA (Ochronotic
POLYPHENOL ACETIC ACID POLYPHENOL Pigment)
OXIDASE OXIDASE
(CU++) (CU++)

HO OH o= =o o= =o

CH2COOH CH2COOH
CH2COOH
n

PHYSICAL
BONDING CHEMICAL
BONDING

CONNECTIVE TISSUE MACROMOLECULES

Adapted from Stanbury, Wyngaarden, & Frederichson Metabolic Basis of Inherited Disease
 Definition

 A gel-like substance found in:

 body cells
 mucous secretions
 synovial fluids
Genetic disorders

Deficiency of enzymes necessary to

breakdown mucopolysaccharides (MPS)

Excessive accumulation of
mucopolysaccharides in body tissues
• Results:
– many serious physical disorders
– Various genetic deformities such as:
• skeletal deformities (especially of the face)
• mental retardation
• decreased life expectancy
 Examples
• Hunter syndrome
• Hurler syndrome
• Scheie syndrome
• Sanfilippo syndrome
• Morquio disease
• Maroteaux-Lamy syndrome
Hurler syndrome (type
I)
Hurler syndrome type I
 Mucopolysaccharidosis I (MPS I) Disease
)Hurler, Hurler-Scheie, Scheie Syndromes(

Key Symptom Images

                                                  

                                                  

                                                  

                                  
Hernia Corneal Coarse Claw hand
clouding facial
features
Causes of the Hurler syndrome

• Inherited as an autosomal recessive

trait
• Metabolic defect: inability
– The body's to make an enzyme:
• lysosomal alpha-L-iduronase
incidence & and risk factors
• Approximately 1 in 150,000 infants
are affected
• Newborn infants with this defect
appear normal at birth
• By the end of the first year, signs of
impending problems begin to
develop
 Prevention
• Genetic counseling: important for parents
with a family history of Hurler syndrome
• Prenatal diagnosis:
• An amniocentesis in the amniotic fluid are
then cultured and the a-L-iduronidase
activity in the cells is determined.
 MPS: Signs
• Hepatomegaly
• Splenomegaly
• Enlarged tongue
• Retinal pigmentation
• Hip dislocation
• Kyphosis
• Heart murmurs
• Heart valve damage from thickening
Tests that may indicate the syndrome
• Increased excretion of dermatan sulfate
and heparan sulfate in the urine

• Absence of lysosomal alpha-L-

iduronidase (in cultured fibroblasts)

• Culture of cells from amniotic fluid

obtained by amniocentesis for enzyme
testing (prenatal testing)
 Tests that may indicate the
syndrome
• Abnormal histological staining of white
blood cells called metachromasia
• X-ray of the skeleten
• X-ray of the spine
• X-ray of the chest
• ECG
Hunter syndrome type II
Sanfilippo syndrome type
III
Sanfilippo syndrome type III
Morquio syndrome Type
IV Skeletal abnormality - hand
Skeletal abnormality: flattened
vertebrae
Maroteaux-Lamy syndrome TypeV
MUCCOPOLYSACCHARIDES
Preventable forms
 Prevention by diet
• Modifying the consumption of certain
dietary compounds can prevent some
monogenic diseases,
• such as galactosemia and phenylketonuria.
• Early diagnosis (Screening!) is basic.
Galactosemia

* characteristics –
galactosemia affects
the body’s ability to
process galactose (a
sugar found in dairy
products)
 Galactosaemia
• Reason: Deficiency of galactose-1-p-uridyl transferase ,
which is essential for galactose metabolism.
• A rare recessive trait
• Galactose-1-phosphate uridyltransferase deficiency,
• Accumulation of galactose in the blood
• Increasing the risk of mental retardation
• Incidence:
– 1/50.000-1/100.000
• Genetic locus: 9p13
• Screening test:
– Lactose-free diet (Soy formula, galactose restricition)
 Mode of Inheritance
* galactosemia –
autosomal recessive
(a child has to inherit
one gene from each
parent that is defective)
* galactosemia is on
chromosome 9
 Punnett Square

• mom = carrier & S s

dad = carrier:
offspring =
25% normal S SS Ss
50% carrier
25% affected
s Ss ss
Symptoms of Galactosemia
* symptoms: kidney
failure, fine and gross
motor skill delays, poor
growth, and mental
retardation (all as a
result of the galactose
build-up)
 Detection of Galactosemia

* Galactosemia appears in approximately 1 in

every 30,000 live births and can be detected
by a blood test
* Galactosemia is a universal genetic disorder
– everyone has equal chances of getting it
 Diagnostic Testing
• At birth, most babies are tested – a small
blood sample is taken from the baby's heel,
and the doctors check for the level of the
GALT enzyme
• Galactosemia can also be detected before
birth, by either: 1)
amniocentesis, or 2) taking a sample of fetal
cells from the placenta
 Prognosis

• if untreated, 75% of all infants with

galactosemia may die
• galactosemia is treatable
 Additional Health Problems
• Galactosemia isn't usually life threatening

• the common health problems include:

cataracts, learning disabilities, poor growth,
and speech disorders
 Treatment
• The only way to treat galactosemia is by
changing one's diet

• People with galactosemia need to stay away

from all foods and drinks that have galactose
(ex: milk, cheese, legumes, which are pods
like peas or beans)
 Genetic Counseling
• For parents who are carriers of galactosemia,
a genetic counselor would show them a
punnett square for galactosemia

• The counselor would also explain that the

chances of the parents' child inheriting
galactosemia are 25% (and a 50% chance of
him/her being a carrier)
 Additional Interesting Facts

• The Duarte variant is another milder,

more common type of galactosemia,
and it affects approximately 1 in 16,000
live births
Nutritional therapy, prevention of
symptoms

• Galactosaemia: Galactose-free diet

• PKU: phenylalanine-restricted tyrosine-

supplemented diet
 PHENYLKETONURIA (PKU)
• What is phenylketonuria (PKU)?
• Who does it affect?
• What are the origins of PKU?
• What are the treatments for PKU?
• What are the precautions of PKU?
 WHAT IS PKU?

PKU (phenylketonuria),
in its "classic" form, is a
rare, inherited metabolic
disease that results in
mental retardation and
other neurological
problems when
treatment is not started
within the first few
weeks of life. .
 PHENYLALANINE
PKU is characterized
by the inability of the
body to utilize the
essential amino acid
phenylalanine.
 WHATS THE DIFFERENCE
BETWEEN ESSENTIAL AND NON-
ESSENTIAL AMINO ACIDS?
Amino acids are the
building blocks for
body proteins.
Essential amino acids can
only be obtained from
the food we eat as our
body does not normally
produce them.
 ENZYMATIC ACTIVITY
• In cases of PKU, the enzyme that breaks down
phenylalanine, phenylalanine hydroxylase, is completely
or nearly completely deficient.

• This enzyme normally converts phenylalanine to another

amino acid, tyrosine, which is utilized by the body.

• When this enzyme, phenylalanine hydroxylase, is absent

or deficient, phenylalanine and its breakdown chemicals
from other enzyme routes, accumulate in the blood and
body tissues.
 LEVELS OF BLOOD
PHENYLALANINE
• A normal blood phenylalanine level is
about 1mg/dl.

• In cases of PKU, levels may range from 6-

80mg/dl, but are usually greater than
30mg/dl.
WHAT HAPPENS WHEN THERE
IS TOO MUCH BLOOD
PHENYLALANINE?

Chronically, high levels of phenylalanine and

some of its breakdown products can cause
significant brain problems. There are other
disorders of hyperphenylalaninemia, but
classic PKU is the most common cause of
high levels of phenylalanine in the blood.
WHAT HAPPENS WHEN THERE
IS TOO LITTLE BLOOD
PHENYLALANINE?
It is important to remember that some
phenylalanine is needed to maintain normal
body function.

Insufficient phenylalanine intake may cause

mental and physical sluggishness, loss of
appetite, anemia, rashes, and diarrhea.
 Phenylketonuria:
• Incidence: 1/10.000
• Reason:
– Deficiency of phenylalanine hydroxilase activity
– prevents conversion of phenylalanine to tyrosine.
– Genetic locus: 12q24.1
– Accumulation of phenylalanine in the blood,
increased risk of neurological damage.
• Screening test:
– Rapid flow fluorimetric assay
• Treatment:
– Dietary restriction of phenylalanine
 WHO DOES PKU EFFECT?

PKU is inherited as
an autosomal
recessive trait.
WHO DOES PKU EFFECT cont’
• Two people who
conceive a child must
both be the carriers of
the defective gene in
order for their child to
have the disorder.

• The “carrier” for PKU

does not have the
symptoms.
WOMEN WITH PKU
It is recommended that
women with PKU who are
of child bearing age,
closely adhere to the low-
phenlyalanine levels before
conception and throughout
pregnancy. The risk of
miscarriage, mental
retardation, microcephaly,
and congenital heart
disease in the child is high
if the mother’s blood
phenylalanine is poorly
controlled.
 INCIDENCE OF PKU
• PKU affects about one out of every 10,000
to 20,000 Caucasian or oriental births. The
incidence in African Americans is far less.

• The PKU disorder is as frequent in men as

it is in women.
WHAT ARE THE SYMPTOMS OF
PKU?
(About 50% of untreated infants have the following early symptoms)

Vomitting
Irritability
Eczema-like rash
Unusual odor to urine
Nervous System Problems(increased muscle tone,
more active muscle tendon reflexes)
Microcephaly
Decreased body growth
 OTHER SYMPTOMS OF PKU
• Prominent cheek and jaw bones widely
spaced teeth

• Poor development of tooth enamel.

 WHAT HAPPENS IF PKU GOES
UNTREATED?
• If PKU goes untreated
or undetected, severe
brain problems occur
such as seizures and
mental retardation.

• This can occur as early

as the second month of
life, if not detected and
treated.
 HOW CAN PKU BE
TREATED?
• Every state now screens the blood
phenylalanine level of all newborns at about
3 days of age.

• This test is one of several newborn

screening tests performed before or soon
after discharge from the hospital.
 HOW CAN PKU BE TREATED
cont’
• Usually a few drops of blood
are obtained by a small prick on
the heel, placed on a card and
then sent for measurement.

• If the screening test is

abnormal, other tests are needed
to confirm or exclude PKU.

• Newborn screening allows

early identification and early
implementation of treatment.
 WHAT TYPE OF DIET IS
APPROPRIATE FOR SOMEONE
WITH PKU?
• The goal of PKU treatment is to maintain the blood
levels of pheylalanine between 2 and 10mg/dl.

• Treatment for PKU consists of a diet low in

phenylalanine, which is maintained infants with
special formulas and in individuals by eliminating
meat and using low protein grain products.
Measured amounts of cereals, starches, fruit, and
vegetables, along with a milk substitute are
recommended instead.
 OTHER THINGS TO STAY
AWAY FROM
• Individuals with PKU
must be alert for food
sweetened with
aspartame.

• NutraSweet in particular,
should be avoided
because it is a derivative
of phenylalanine.
 HELPFUL WEBSITES FOR LOW
PROTEIN FOODS
*http://
www.cambrookefoods
.com/

http://
www.waisman.wisc.ed
u/foods/
lowprotein.html
LIFESTYLE ADJUSTMENTS FOR
PKU PATIENTS
• More frequent doctor visits
• Required dietary restrictions that may
impact day to day activities.
• Permanent monitoring of blood
phenylalanine levels
 Sex-linked genes in humans

• Some genes on X-chromosome code for female

traits; some genes on Y chromosome code for
male traits
• X chromosome has 164 million bases; Y
chromosome has 59 million bases
• Current estimate of X-linked genes range from
729-748
• Current estimate of Y-linked genes is 78
 X-inactivation in female mammals
• In mammalian females, one of the two X
chromosomes in each cell is randomly
inactivate during embryonic development
• As a result, the cells of females and males
each the same effective dose of genes with
loci on the X chromosome
• The inactive X in each cell of a female
condenses into a compact object, called a
Barr body
 Alterations of chromosome number or
structure cause some genetic disorders

Errors during meiosis can change the number

of chromosomes per cell or the structure of
individual chromosomes
Such alterations can affect phenotype
 X-Linked Disorders
• Pedigree charts show the inheritance pattern for
X-linked recessive disorders:
– more males than females have the trait because
recessive alleles on the X chromosome are
expressed in males
– a grandfather passes an X-linked recessive disorder
to a grandson through a carrier daughter
• X-linked recessive disorders include: red-green
color blindness, muscular dystrophy,
hemophilia
 Color Blindness
• Three types of cones are in the retina
detecting red, green, or blue.
• Genes for blue cones are autosomal; those
for red and green cones are on the X
chromosome.
• Males are much more likely to have red-
green color blindness than females.
• About 8% of Caucasian men have red-green
color blindness.
X-linked Inheritance – When Men and Woman Play by Different Rules

Behind the 8-ball? Colorblindness is an X-linked recessive trait.

 Muscular Dystrophy
• Muscular dystrophy is characterized by the
wasting of muscles.
• Most common form is Duchenne muscular
dystrophy, occurring in 1 of 3,500 males born
in U.S.
• Muscles weaken, frequent falls and difficulty
in rising occur early; death occurs by age 20
• Duchenne Muscular
Dystrophy
– 1 boy in every 3,000
– progressive weakening
of muscles and loss of
coordination
– more common in males
 Fragile X Syndrome
• Second most common cause of mental
retardation (after Down syndrome)
• Cytogenetic abnormality appears as a
constriction in the long arm of X-chromosome
during folate deficient culture conditions
• Mutation is present in an untranslated portion
of the Familial Mental Retardation Gene
(FMR-1)
• Loss of function mutation
 Pedigrees
• A pedigree is a diagram of family relationships that uses symbols
to represent people and lines to represent genetic relationships.

• These diagrams make it easier to visualize relationships within

families, particularly large extended families.

• Pedigrees are often used to determine the mode of inheritance

(dominant, recessive, etc.) of genetic diseases.

• Scientists or a genetic counselor would find out about your family

history and make this chart to analyze.
 Why do Pedigrees?
Punnett squares and chi-square tests work well for
organisms that have large numbers of offspring and
controlled matings, but humans are quite different:
• The human generation time is about 20 years.
• Humans produce relatively few offspring compare to
most other species.
• Well-planned breeding experiments are impossible.
• Small families. Even large human families have 20
or fewer children.
• Uncontrolled matings, often with heterozygotes.
• Failure to truthfully identify parentage.
 Goals of Pedigree Analysis

1. Determine the mode of inheritance: dominant,

recessive, partial dominance, sex-linked, autosomal,
mitochondrial, maternal effect.
2. Determine the probability of an affected offspring for a
given cross.
3. In humans, pedigree analysis is used to determine
individual genotypes and to predict the mode of
transmission of single gene traits.
4. Pedigree analysis is used to study single gene disorders,
such as Huntington’s Disease, a progressive
neurodegenerative disorder
Basic Symbols
More Symbols
 Pedigree
• third generation lacks a widow’s peak, but both her parents
have widow’s peaks, then her parents must be heterozygous
for that gene
Not bent little fingers Bent little fingers
Non-hitchhiker’s thumb Hitchhiker’s
thumb
 Non pigmented iris

Pigmented iris
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