Genetics terms you need to know:

 Gene – a unit of heredity;

a section of DNA sequence
encoding a single protein
 Genome – the entire set
of genes in an organism

 Alleles – two genes that occupy the same

position on homologous chromosomes and that
cover the same trait.
 Locus – a fixed location on a strand of DNA
where a gene or one of its alleles is located.
 Homozygous – having identical genes (one
from each parent) for a particular characteristic.
 Heterozygous – having two different genes for
a particular characteristic.

 Dominant – the allele of a gene that masks or

suppresses the expression of an alternate
allele; the trait appears in the heterozygous
condition.
 Recessive – an allele that is masked by a
dominant allele; does not appear in the
heterozygous condition, only in homozygous.
 Genotype – the genetic makeup of an
organisms
 Phenotype – the physical appearance
of an organism
 Monohybrid cross
 Parents differ by a single trait.
A & a = dominant & recessive alleles of the
same gene

AA = homozygous for dominant

aa = homozygous for recessive
Aa = genotype heterozygous,
phenotype dominant
 Mendel’s Principles
 1. Principle of Dominance:
- one allele might mask the phenotypic expression of the
other, then tis allele is dominant, the other allele is
recessive
 2. Principle of Segregation:
- when gametes are formed, gene pairs segregate, each
gamete gets only one gene
- If each parent is homozygous for two different alleles of
the same gene, all offsprings show dominant phenotype
- If both parents are heterozygous to the same gene, a
parent has a 50% chance of passing each allele to the
offspring
3. Principle of Independent Assortment:
“Members of one gene pair segregate
independently from other gene pairs during
gamete formation”

Exception to this law???????

 Mendelian disorders could be inherited in 5 ways:
- AD
- AR
- X-LR
- X-LD
- Y-linked.
 Family studies necessary to determine the mode of
inheritance of a feature or disorder, for appropriate
genetic counseling.
 Family studies are recorded in the form of pedigree
charts
 Pedigree
 Pedigree: short hand system
of recording pertinent
information about a family.
 Proband (Index case;
propositus/ proposita): Patient
through whom an affected
family is first brought to the
attention of the geneticist
 Position of proband indicated
by an arrow.
 Consultand: person who
brings the family to attention
of the geneticist
 Isolated case: Only one
affected member in a family
 Sporadic case: isolated case
due to new mutation
 Pedigree …
 Kindred: extended family of the proband
 Sibs: brothers & sisters
 Sibship: A family of sibs
 First degree relatives: Parents, sibs and offsprings of the proband
 Second degree relatives: grandparents, grandchildren, uncles,
aunts, nephews, nieces, half-sibs of proband
 Consanguineous: couple who has one or more ancestors in
common
 “First cousin once removed” ???

Note: Information about entire family, sibship & kinship for a minimum
3 generations, has to be recorded, for a pedigree analysis
Draw a pedigree chart with the
following family history
 Proband is affected female, married to unaffected male
 Her father is affected, mother is unaffected
 Her paternal grandmother is affected, paternal
grandfather unaffected
 Her father has 3 siblings:
− Unaffected elder brother, married to unaffected female,
they have a unaffected child
− Younger sister, married to unaffected male, they have an
unaffected daughter and two affected sons
− Unaffected youngest brother, unmarried
 Single gene disorders
 Mendelian inheritance applies in humans for single gene
disorders
 A trait or a disorder, determined by a single gene on an

autosome – shows autosomal inheritance.

 Types: Autosomal dominant (AD)

& Autosomal recessive (AR)

 A trait or a disorder, determined by a single gene on one

of the sex chromosomes - shows sex- linked inheritance.

 Types: X- linked recessive (X- LR)

X - linked dominant (X-LD)

Y- linked inheritance.
 AD- Features
• Manifests in the heterozygous state
• Phenotype present in successive generations
• Pattern of inheritance referred as ‘vertical’
transmission.
• Both the sexes equally affected.
• All forms of transmission between sexes seen:
- male to male,
- male to female,
- female to female,
- female to male.
 AD- Features …
- Genetic risk: Any child born to a person affected with
AD trait or disorder has a 1 in 2 (50%) chance of inheriting
it & being similarly affected.
- AD disorders usually can’t be transmitted through
unaffected parents.
- Usually AD conditions are due to structural protein
defects.
Punnett’s square showing possible
gamete combination for an AD
allele - Affected -
parent

Normal D d
parent
d Dd dd
d Dd dd
 Segregation of AD trait
(one parent affected)

 
Affected Normal
father mother
Dd dd

  
Dd dd dd
Dd

Affected Normal Affected Normal

Son Daughter Daughter Son

(25%) (25%) (25%) (25%)

 Segregation of AD trait
(Both parents affected)

 
Affected Affected
father mother
Dd Dd


DD Dd Dd
dd

Severely
Affected Affected Normal
Affected
(25%) (25%) (25%)
Pedigree showing AD inheritance

1
 AR- Features
- Accounts for >30% of the single gene disorders.
- AR traits & disorders manifest when mutant allele
present in double dose i.e homozygous state.
- Individuals heterozygous for AR mutant allele
show no features of the disorder, healthy & known
as carriers.
- Affected individuals in a family, usually in a
single sibship i.e brothers & sisters - ‘horizontal’
transmission.
 AR- Features

-Both the sexes are equally affected.

- Because of which all forms of transmission between
sexes are seen: male to male, male to female, female to
female, female to male.
- Genetic risk: The children of 2 carriers have a 1
in 4 (25%) of being normal; a 1 in 2 (50%) chance of being
carrier & 1 in 4 (25%) chance of being
affected.
- Consanguinity may be observed between the parents or
in the family.
Punnett’s square showing possible gamete
combination for heterozygous carrier parent of
an AR allele

- Affected -
parent

Normal d d
parent
D Dd Dd
D Dd Dd
 Segregration of AR trait
(both parents carriers- heterozygous)


Carrier
father
Rr
 Carrier
mother
Rr

rr

  
Rr Rr
RR

Normal Affected
Carrier (50%)
(25%) (25%)
 Segregration of AR trait
(one parent carrier )


Carrier
Father
Rr
 Normal
mother
RR

Rr

 
RR Rr RR

Normal Carrier Normal Carrier

(25%) (25%) (25%) (25%)
Pedigree showing AR inheritance
 X – LD features

 Uncommon, but disorders, which manifest in the

heterozygous female as well as in the male, who has the
mutant allele on his single X chromosome.
 Genetic risk:
- Both the daughters & the sons of an affected female
with X-LD disorder, have 1 in 2 (50%) chance of being
affected.
- Affected male transmit the trait to the daughters but
none to his sons.
- An excess of affected females may be seen in families
with X-LD disorders.
Pedigree showing X-LD inheritance
 X-LR Features

 X-LR trait determined by a gene carried on X

chromosome & usually manifests only in males.
 A male with a mutant allele on his single X, said to be
hemizygous.
 X-LR diseases transmitted by healthy heterozygous
female carriers to affected male .
 Also transmitted by affected males to their obligate
carrier daughters with a consequent risk to male
grandchildren through daughters.
 X-LR Features …

 This type of pedigree referred to as a ‘diagonal or a

knight’s move’ pattern of transmission.
 A male can’t transmit X-linked trait to his son.

 Genetic risk:

- A male transmits his X to his daughters and Y to his

sons.
- An affected male has children with a normal female as
his partner, all his daughters will be obligate carrier, but
none of his sons will be affected.
 X-LR Features …

 Genetic risk:

- For a carrier female of X-LR trait having children with

a normal male, each son has a 1 in 2 (50%) chance of
being affected & each daughter has 1 in 2 (50%) chance
of being a carrier.
 X-L disorders not compatible with survival to the

reproductive age & not therefore transmitted by affected

males.
 X-LR Features …

 Females affected with X-LR traits, because of

homozygosity or skewed X- inactivation or numerical X
chromosome abnormalities and X-autosome
translocation.
 In hetrozygous females, variable expression is seen

for the manifested features.

 Mating diagram: X-LR

Affected
father

Xr Y
 X X
Normal
Mother

X Xr X Y X Xr X Y

Carrier

Normal
 
Carrier Normal
Daughter Son Daughter Son
(25%) (25%) (25%) (25%)
 Segregation of gene: X-LR

Normal
father  X Y
 X Xr
Carrier
mother

X X X Y X Xr Xr Y

Normal

Normal
 
Carrier Affected
Daughter Son Daughter Son
(25%) (25%) (25%) (25%)
Pedigree showing X-LR inheritance
X-inactivation

 Y-chromosomes carry only 30 protein coding

genes but X carrries hundreds of protein coding
genes
 To equalise the amount of X-linked proteins in
males and females, the mechanism that exists is
X-inactivation
 Occurs in blastocyst stage in females
 One of the two X-chromosomes is inactivated by
getting converted to highly condensed
heterchromatin, appears as barr body
Features of X-inactivation

 Random
 Fixed
 Incomplete
 Only one X chromosome active in any cell,
even in aneuploidy
 Caused by XIST gene – produces mRNA that
coats the X chromosome, inactivates it;
inactivated X chromosome converted to
heterochromatin; gene regions are methylated
Manifesting heterozygotes

 In X-linked recessive inheritance, sometimes

heterozygotes show symptoms of the disease
 Such females are called manifesting
heterozygotes
 Happens if most of the X chromosomes with
normal alleles are inactivated
 Disease pattern is milder compared to
hemizygous males because atleast some X
chromosomes have normal alleles
 Y – linked or holandric inheritance implies that only
males affected.
 Affected male transmits Y –linked trait to all his sons,

but none to the daughters.

 Y- linked genes:

=SRY genes: sex determining regions in Yp.

=Genes involved in spermatogenesis in Yq:
AZFa, AZFb, AZFC:
- Normal sperm development

- Absence of the 3 loci – infertility

Exceptions to Mendelian pattern of
inheritance
 Mitochondrial inheritance & heteroplasmy
 New mutation and mosaicism
 Pseudodominance
 Reduced penetrance
 Variable expressivity
Patterns of Inheritance
not described by Mendel
 still follow Mendel’s laws
 Incomplete dominance
 Codominance
 Pleiotropy
 Epistasis
 Polygenic inheritance
 Multifactorial inheritance
Polygenic Inheritance
 An additive effect of 2 or more
genes on one character
example
skin pigmentation

 at least 3 genes

hair color

 at least 4 genes
Multifactorial Inheritance

 Genotype does not rigidly define the phenotype,

but a range of possibilities over which the
environment can influence

 genes + environment & diet phenotype

Phenotype depends on environment
and genes
 Humans: nutrition influences height, exercise alters
build, sun-tanning darkens the skin, and experience
improves performance on intelligence tests.
 Identical twins: genetic equals, accumulate
phenotypic differences as a result of their unique
experiences.
 MFI …

 MFI disorders:
 Congenital malformations: Cleft lip/ palate, congenital
dislocation of hip, congenital heart defects, neural tube
defects, pyloric stenosis,
 Acquired diseases of childhood & adult life: asthma,
autism, diabetes mellitus, epilepsy, glaucoma,
hypertension, ischaemic heart disease, manic depression,
schizophrenia.
 MFI …

 Genetic risk:
Recurrence risk to relatives of MFI are influenced by

- the disease severity,

- the degree of relationship to the index case,
- the
number of affected close relatives,
- if a higher incidence in one sex &
- the sex of the index case.
 MFI …
 Severity:
Cleft lip/ palate: Unilateral 2%, Bilateral 6%.
 Relationship:
Spina bifida: 1st to 3rd: 4 to 0.5%.
 More than one affected child: 10%.
 Particular sex:
Pyloric stenosis: M:F = 5:1;
Male’s male offsprings: 5.5% & female offsprings
2.4%;
Female’s male child: 19.4% & female child 7.3%.
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance
Identify the following pattern of
inheritance