Inheritance Transmission and Penetrance

8/3/2019 Inheritance Transmission and Penetrance

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V.FEMINA KOKILA

PG STUDENT

DEPARTMENT OF ORAL PATHOLOGY

RAGAS DENTAL COLLEGE



Agenda Introduction

Terminologies

Mendelian inheritance Non mendelian inheritance

Expression

Penetrance

Chromosomal abnormalities

Reference



TerminologiesGene : Is a stretch of DNA whose sequence determines the structure and function

of a specific functional molecule (usually a protein)

Genotype: The set of alleles which make up an individuals genetic constitution

Phenotype: The appearance of an individual which results from the interaction of environment and genotype

Homozygous: If both homologous chromosomes carry the same allele at a given genelocus

Heterozygous: If two homologous chromosomes carry different alleles at a givenlocus



Locus: Chromosomal position where DNA for a specific geneis present

Mutation: Irreversible or permanent DNA damage

Dominant : Alleles that determine the phenotype displayed

a heterozygote with another (recessive) allele.

Recessive : A gene that phenotypically manifest in thehomozygous state but is masked in the presenceof a dominant allele.

Allele: Alternative form of gene found in the same locus of homologouschromosomes

Carrier : An individual heterozygous for a single recessive gene.

Trait : Any detectable phenotypic property of an organism.

Contd . . .



INHERITANCE

Inheritance is the process by which the characteristics of individuals are passed

to their offspring

Genes encode these characteristics

A gene is a unit of heredity that encodes information for the form of

a particular characteristic



Principle of segregation: Each gamete carries only one allele for seedshape, because the alleles have segregated during meiosis.

Principle of independent assortment: the genes for seed shape and color assortindependently because they are located on different chromosomes

Law of Segregation and Independent assortment



P

R

I

N

C

I

P

L

E

OF

D

O

MI

N

A

N

CE



MODES OFINHERITANCE

MENDELIAN INHERITANCE

AUTOSOMAL

-DOMINANT

-RECESSIVE

SEX LINKED

-X LINKEDDOMINANT

-X LINKEDRECESSIVE

NON MENDELIANINHERITANCE

POLYGENICINHERITANCE

CHROMOSOMAL ABNORMALITIES



PUNNET SQUARE PEDIGREE CHART

Affected parent ( A a)

N o r m a l p a r e n t ( a a )

Gametes

G a m e t e s

a

a

a A

A a a a

a a

Affected

Normal

Normal

A a Affected

METHODS OF ILLUSTRATING INHERITANCE



Pedigree chart

5

n n

6 5

n

Normal male,female, unknown sex

Affected individual

multiple

More than 2

Unknown number

Deceased/ still birth

proband

abortions

Termination of pregnency

mating

No relation

consanguineous

Parents known

Parentsunknown

No children

AdoptedIn

Adopted

Out



Affected parent ( A a)

N o r m

a l p a r e n t ( a a

)

Gametes

G a m e t e s

a

a

a A

A a

a a

a a

Affected

Normal

Normal

A a

Affected

AUTOSOMAL DOMINANT



AUTOSOMAL DOMINANT

Amelogenesis Imperfecta

Dentinogenesis Imperfecta

Dentin Dysplasia

Osteogenesis Imperfecta Aperts Syndrome Crouzons Syndrome Mandibulofacial Dysostosis

Neurofibromatosis

Huntington disease Achondroplasia

Ehlers Danlos Syndrome

Epidermolysis Bullosa



Normal heterozygote

parents ( A a)

N o r m a l h e t e r o z y g o t e

p a r e n t s (

A a )

Gamete

G a m

e t e s

A

A a

a a Affected

Normal

A

a A a

A A

Carrier

Carrier

AUTOSOMAL RECESSIVE

a



AUTOSOMAL RECESSIVE Tay-Sachs Disease

Cystic Fibrosis

Phenylketonuria

Sickle-cell Disease

Xeroderma pigmentosum

AUTOSOMAL DOMINANT AUTOSOMAL RECESSIVE

Parents will be affected Parents will be usually carriers

Each child is under 50% risk Each child is under 25% riskMode of transmission is vertical Usually skip generation

New mutations are common More common with consanguinity



Gametes

G a m e t e s

a

A a

a a Affected

A

a

N

o r m a l h e t e r o

z y g o t e

p a

r e n t s ( A a )

A aCarrier

Carrier

a

Affected homozygote parents (aa)

a a Affected

PSEUDO DOMINANCE CODOMINANCE



LyonizationProcess of random inactivation of one of the sex chromosome (X)in females



Gametes

G a m

e t e s

Y

X Y X

X

N o r m a l F e m a l e ( X X )

X X Affected

X

Affected Male (X Y )

X X X Y Normal Affected

Normal

X- LINKED DOMINANT



Gametes

Y

X Y X

X

A f f e c t e d F e

m a l e ( X X )

X X Affected

X

Unaffected Male (XY)

X X X Y NormalNormal

Affected

•Expressed in heterozygotes

• Lethal in hemizygotes

• Often affects females

• Affected father cannot transmit tothe sons

• Affected father transmit disorder tothe daughters

ExamplesIncontinentia Pigmenti Vitamin D Resistant Rickets



C a r r i e r F

e m a l e

( X X )

Gametes

G a m e t e s

Y

X Y Affected

X

X

X XCarrier

Normal

X

Normal Male (XY)

X X XY

Normal

X-LINKED RECESSIVE



G a m e t e s

Y

X Y Normal

X

X

X Xcarriers

Normal

Affected Male (X Y)

X X XY

carriers

X

N o r m a l

F e m a l e ( X X )

•Expressed in all males but only in

homozygous females

• Transmitted from affected manthrough his daughter

• No male to male transmission

• Daughters are heterozygouscarriers

EXAMPLES•Color Blindness•Hemophilia A•Dyskeratosis Congenita



Y – linked inheritance

Hypertrichosis Icththyosis



Polygenic inheritance Inheritance of a phenotype determined by many genes at different loci, with

each gene exerting a small additive effect Additive implies the effects of genes are cumulative, i.e no one gene is

dominant or recessive E.g. : Height, weight, skin color if height was determined by two alleles, a for tall and b for short at a single

locus-3 groups are possible with a ratio 1:2:1

1 tall-aa2 average height-ab3 short-bb

Cleft palate Hare lip and cleft palate Cardio-vascular disesases Schizophrenia Diabetes

NON MENDELIAN INHERITANCE



MITOCHONDRIAL INHERITANCE



PENETRANCE

The proportion of genotypes thatactually show expected phenotypes iscalled penetrance

Help us predict how likely is that a trait

expresses.

Less than 100% penetrance -incompletepenetrance

eg: osteogenesis imperfecta (OI).



EXPRESSION

Expressivity is the degree to which trait

expression differs among individuals.

Expressivity describes individual

variability

Example: Marfan syndrome



Amelogenesis Imperfecta

Hypomaturation HypoplasticHypomaturation

Hypoplastic-Pitted Hypocalcified Hypocalcified

Expression Contd….



Dentinogenesis Imperfecta

Expression Contd….



Chromosomal Disorders Single Chromosome Disorders 1. Deletion

• Genetic material ismissing

2. Duplication

• Genetic material ispresent twice

3. Inversion• Genetic material is

“flipped”

http://upload.wikimedia.org/wikipedia/commons/0/01/Single_Chromosome_Mutations.png



Two Chromosome Disorders

Insertion

• Genetic material is added from anotherchromosome

Translocation

• Material is swapped with anotherchromosome



HUMAN DISORDERS DUE TO CHROMOSOME ALTERATIONS IN AUTOSOMES

Down syndrome Trisomy 21

Patau syndrome Trisomy 13

Edward's syndrome Trisomy 18

HUMAN DISORDERS DUE TO CHROMOSOME ALTERATIONS IN SEX CHROMOSOMES

Trisomy X 47, XXX females

Klinefelter syndrome 47, XXY males

Monosomy X (Turner's syndrome) 45,XO females

ALTERATIONS IN CHROMOSOME STRUCTURE

Deletion Cri du chat (cry of the cat)

Duplication Fragile X

Translocation Acute Myelogenous Leukemia

Inversion Four ring syndrome

CHROMOSOMAL DISORDERS



GENETIC DISORDERS MAY NOW BE DETECTED EARLY

Testing Fetal Cells Amniocentesis - long needle withdraws a small amount of the

fluid that surrounds the fetus and contains a few fetal cells Chorionic Villi Sampling (CVS) - tube is inserted through the

vagina into the uterus and fetal cells are obtained by suction Testing the Embryo

A single cell can be removed from the 8-celled embryo andsubjected to preimplantation genetic diagnosis (PGD)

Testing the Egg

Polar bodies (nonfunctional cells produced during egg formation)receive a haploid number of chromosomes When a woman is heterozygous for a recessive genetic disorder,

about half the polar bodies have received the mutated allele, whilethe egg has received the normal allele



REFERENCES Emery’s Elements of medical genetics-11th edition

Robins Pathologic Basis of Disease-7th edition

Genes viii-8th edition

Neil E. Lamb, American College of Medical Genetics

The Australasian Genetics Resource Book – 2007

SK Agarwal, S Khatri, N Prakash, NP Singh, S Anuradha,

A Prakash , Maturity Onset Diabetes of Young. JIACM 2002; 3(3): 271-7

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Inheritance Transmission and Penetrance