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

Terminologies
Gene : 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 gene
locus

Heterozygous: If

two homologous chromosomes carry different alleles at a given locus

Contd . . .
Locus: Chromosomal position where DNA for a specific gene is 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 the homozygous state but is masked in the presence of a dominant allele.
Allele: Alternative form of gene found in the same locus of homologous chromosomes

Carrier : An individual heterozygous for a single recessive gene. Trait : Any detectable phenotypic property of an organism.

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

Law of Segregation and Independent assortment

Principle of independent assortment: the genes for seed shape and color assort independently because they are located on different chromosomes Principle of segregation: Each gamete carries only one allele for seed shape, because the alleles have segregated during meiosis.

P R I N C I P L E O F D O M I N A N C E

MODES OF INHERITANCE

MENDELIAN INHERITANCE

NON MENDELIAN INHERITANCE

AUTOSOMAL
-DOMINANT -RECESSIVE

SEX LINKED
-X LINKED DOMINANT

POLYGENIC INHERITANCE

CHROMOSOMAL ABNORMALITIES

-X LINKED RECESSIVE

METHODS OF ILLUSTRATING INHERITANCE

PUNNET SQUARE
Affected parent (Aa) Gametes

PEDIGREE CHART

A Aa
Affected

a aa
Normal

Normal parent(aa)

a
Gametes

Aa
Affected

aa
Normal

Pedigree chart
Normal male, female, unknown sex Affected individual More than 2 Parents known 5 6 5 multiple mating No relation consanguineous

n Unknown number
Deceased/ still birth proband

Parents unknown

No children

abortions Termination of pregnency Adopted In Adopted Out

AUTOSOMAL DOMINANT

Affected parent (Aa) Gametes

A
Normal parent(aa) Gametes

Aa
Affected

Normal

aa

Aa
Affected

aa
Normal

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

AUTOSOMAL RECESSIVE

Normal heterozygote parents (Aa) Gamete

Normal heterozygote parents (Aa) Gametes

A A AA

a Aa aa

Normal

Carrier

Carrier

Aa

Affected

AUTOSOMAL RECESSIVE

Tay-Sachs Disease Cystic Fibrosis Phenylketonuria Sickle-cell Disease Xeroderma pigmentosum

AUTOSOMAL DOMINANT Parents will be affected Each child is under 50% risk Mode of transmission is vertical

AUTOSOMAL RECESSIVE Parents will be usually carriers Each child is under 25% risk Usually skip generation

New mutations are common

More common with consanguinity

PSEUDO DOMINANCE

CODOMINANCE

Affected homozygote parents (aa) Gametes

a
Normal heterozygote parents (Aa) Gametes

a Aa aa
Affected

A a

Carrier

Aa
aa

Carrier

Affected

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

X- LINKED DOMINANT

Affected Male (XY) Gametes X Y

Normal Female (XX) Gametes

X X

Affected

XX

XY
Normal

XX
Affected

XY
Normal

Expressed in heterozygotes

Unaffected Male (XY) Gametes X Y

Lethal in hemizygotes
Often affects females Affected father cannot transmit to the sons Affected father transmit disorder to the daughters

Affected Female (XX)

X X

Affected

XX

Affected

XY

XX
Normal

XY
Normal

Examples Incontinentia Pigmenti Vitamin D Resistant Rickets

X-LINKED RECESSIVE

Normal Male (XY) Gametes X

Carrier Female Gametes (XX)

XX
Carrier

XY
Affected

XX
Normal

XY
Normal

Affected Male (XY) X Y

Expressed in all males but only in homozygous females

Transmitted from affected man through his daughter

Normal Female (XX) Gametes

No male to male transmission

XX
carriers

XY
Normal

Daughters are heterozygous carriers

XX
carriers

XY
Normal

EXAMPLES Color Blindness Hemophilia A Dyskeratosis Congenita

Y linked inheritance
Hypertrichosis Icththyosis

NON MENDELIAN INHERITANCE

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-aa 2 average height-ab 3 short-bb

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

MITOCHONDRIAL INHERITANCE

PENETRANCE
The proportion of genotypes that actually show expected phenotypes is called penetrance

Help us predict how likely is that a trait expresses. Less than 100% penetrance -incomplete penetrance eg: osteogenesis imperfecta (OI).

EXPRESSION
Expressivity is the degree to which trait expression differs among individuals.

Expressivity describes individual variability

Example: Marfan syndrome

Expression Contd.

Amelogenesis Imperfecta
Hypomaturation Hypomaturation Hypoplastic

Hypoplastic-Pitted

Hypocalcified

Hypocalcified

Expression Contd.

Dentinogenesis Imperfecta

Chromosomal Disorders
Single Chromosome Disorders
1. Deletion
Genetic material is missing

2. Duplication
Genetic material is present twice

3. Inversion
Genetic material is flipped

Two Chromosome Disorders

Insertion
Genetic material is added from another chromosome

Translocation
Material is swapped with another chromosome

CHROMOSOMAL DISORDERS
HUMAN DISORDERS DUE TO CHROMOSOME ALTERATIONS IN AUTOSOMES Down syndrome Patau syndrome Edward's syndrome Trisomy 21 Trisomy 13 Trisomy 18

HUMAN DISORDERS DUE TO CHROMOSOME ALTERATIONS IN SEX CHROMOSOMES Trisomy X Klinefelter syndrome Monosomy X (Turner's syndrome) 47, XXX females 47, XXY males 45,XO females

ALTERATIONS IN CHROMOSOME STRUCTURE

Deletion
Duplication Translocation Inversion

Cri du chat (cry of the cat)

Fragile X Acute Myelogenous Leukemia Four ring syndrome

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 and

subjected 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, while the egg has received the normal allele

REFERENCES
Emerys 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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