Classnote_Pedigree Analysis

Mendelian Analysis in Humans

The problems encountered in human genetic inheritance are :
While some are genetically relatively simple and follow the pattern of Mendelian inheritance, most
traits are affected by more than one gene and cannot be analyzed using simple Mendelian genetics.
Many single gene traits that can be followed cause rare diseases rather than common phenotypes.
Genetics is not straightforward in humans because there are :
1. No true-breeding humans
2. Generation time is long (impractical)
3. Controlled matings
4. Siblings rarely mate to generate F2
5. Small family sizes
Pedigrees help us infer if a trait is from a single gene and if the trait is dominant or recessive.
Therefore, in humans, we must use pedigrees to study inheritance.
A pedigree is an orderly diagram of a family’s relevant genetic features extending through
multiple generations that uses symbols and lines to represent individuals and genetic relationships.
Rare traits can be studied by carefully analyzing families that are affected. The trait may be rare in
the population but common in a particular
family.
Analysis of pedigrees using knowledge of
Mendelian principles allows us to determine
(i) whether the trait has a dominant or
recessive pattern of inheritance, and (ii)
whether the gene in question is located on X
or Y chromosome or on an autosome. This
kind of information can be used to predict
risk.
Symbols
The symbols used in the pedigree chart are
given alongside.
Rules of Pedigree Analysis
Don't guess !
1. Every gamete carries exactly one allele
for every gene. Exception: Sex linked genes
in males.
2. Any individual with the recessive
phenotype (appearance) must be homozygous
recessive.
3. Any individual with a homozygous
recessive offspring must have at least one
recessive allele.
4. Any individual with a homozygous recessive parent must have at least one recessive allele.
Steps of Pedigree Analysis
Pedigree analysis proceeds in several steps:
Rule out patterns of inheritance that are inconsistent with the pedigree.
If only one pattern of inheritance is consistent with the pedigree, it is accepted as the pattern for
that trait.

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The basic modes of inheritance are : Autosomal dominant / recessive, X-linked dominant /
recessive, Y-linked, mtDNA-linked (which we will not consider for your convenience).

Inheritance Key Features

Pattern

Autosomal Affected individuals must carry at least one dominant allele (heterozygotes show the
Dominant phenotype).
Unaffected parents will never produce affected offspring (unless a new mutation
occurs).
Affected individual must have at least one parent with the trait.
Two affected parents may produce non-affected child (this NEVER happens in
recessive traits).
Condition must appear in every generation.
Condition often occurs in matings of related individuals.
Examples : Achondroplasia, Huntington Disease, Arrthymogenic Right Ventricular
Dysplasia Type 5 (ARVD5), Hereditary nonpolyposis colorectal cancer, ACHOO
syndrome - photic sneezing, Fatal Familial Insomnia.

Autosomal Affected individuals are homozygous recessive.

Recessive Unaffected parents can have affected offspring (this can NEVER happen in
dominant traits).
All progeny from two affected parents are always affected.
For an affected offspring from unaffected parents, both parents need to be
carriers (heterozygous).
Examples : Oculocutaneous albinism, Batten Disease, PTC tasting.

X-linked Affected males always pass the trait to all daughters and never to their sons.
Dominant An affected individual must have at least one affected parent.
Affected females are usually (but not always) heterozygous.
D-D-D rule : If trait is Dominant, and Dad is affected, then all Daughters will be
affected.

X-linked Affected females produce only affected sons.

Recessive Criss-Cross inheritance: affected males & females alternate among generations.
Expect half the sons of unaffected female carriers to be affected.
More males than females show the phenotype.
NONE of the progeny of affected male show the phenotype (unless mother is
carrier / affected) since affected males pass the allele to ALL daughters but
NEVER to their sons.
ALL daughters of affected male are carriers (heterozygotes).
Daughter will show phenotype ONLY IF both mother and father have the allele.
Affected females pass the allele to ALL their sons.
Heterozygous female (carriers) pass the allele to HALF their sons and HALF their
daughters.
Examples : Hemophilia A, Testicular Feminization Syndrome, Red-Green Colour
Deficiency.

Y-linked Fathers transmit to all their sons but none of their daughters.
No Y linked genes are convincingly associated with nonsexual phenotypic variants.

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Examples of Possible Nonsex Y linked gene are : Hairy Ear Rim gene: proposed to be
caused by a Y linked gene - extremely rare in most countries but less rare in India.

EXAMPLES
Schwartz-Jampel syndrome
(AUTOSOMAL RECESSIVE)

Cutaneous malignant melanoma (AUTOSOMAL

DOMINANT)

Charcot-Marie-Tooth disease (X LINKED

RECESSIVE)

Heterotopia (X LINKED
DOMINANT)

Useful Tips :
a) If both parents of an affected child are normal, then it is recessive.
b) If each generation has the trait, then Trait is dominant.
c) When father is affected and son is also affected, then the trait is "Autosomal
Dominant".