MODES OF INHERITANCE

PATTERN OF SINGLE GENE INHERITANCE

Main categories of genetic disorders

•Chromosomal

•Single gene

•Multifactorial

Inherited variation in the genome is the cornerstone of human genetics.

Terms used

•Alleles

•Genotype

•Phenotype

•Homozygous

•Heterozygous

•Mutation

•Single gene disorder –

1)specific allele at a locus

2)or both members of homologous pair

Modes of Inheritance

•Describes the different ways the genes are handed down

•Genes exists in pairs on homologous chromosomes except X & Y

•X & Y have few loci carrying homologous genes

•An inherited trait depends on

1)Single gene –Mendelian inheritance

2)Cumulative effect of no. of genes – Polygenic

•Mendelian inheritance - 1)Autosomal 2)Sex –linked

•Dominant inheritance (Phenotype) expressed in heterozygotes &homozygotes.

•Recessive inheritance expressed in homozygotes

•Codominant inheritance - AB Blood group

•Intermediate inheritance –

Sickle cell trait-Partial expression of both alleles

•X-linked trait 1) Males - hemizygous

2)Females – heterozygotes show

variable expression

•Y- linked trait - holandric inheritance

PATTERN OF TRANSMISSION OF SINGLE GENE DISORDER

To establish the pattern

1)Obtain Family history - Pedigree chart is prepared. A shorthand method of recording the pertinent information about the family. There are standard symbols used for drawing a pedigree.

2)It depends on a)Chromosomal location of gene

- autosomal or sex-linked

b)Phenotype – dominant or recessive

Factors affecting pedigree pattern –

•Small family size

•Chance segregation of genes from parents to children.

•New mutations.

•Variable expression of genes.

•Effect of other genes & environment on gene expression.

•Failure of some genotypes to survive.

•Lack of accurate information about the presence of disease in relatives

Autosomal Dominant InheritanceAn autosomal dominant trait expresses in a heterozygote state. Homozygotes of it are severely affected because of double dose of an abnormal gene.Pedgree charting of autosomal dominant inheritance

1. An affected person has an affected parent, exception being mutant gene.

2. An affected person has normal and abnormal offsprings in equal proportions, i.e. there is 50% chance of dominant trait being transmitted to offsprings from affected parents.

3. Both males and females are equally affected.

4.The trait appears in every generation without skipping. An exception to this could be the trait impairing reproductive capacity of an affected person.

5.Normal children of affected person do not transmit the disease.

Features associated with autosomal dominant inheritance

•Delayed onset

•Variable expression & Penetrance

•Pleiotropy -Single gene and multiple phenotypic effects

•New mutation

•Genetic heterogeneity

AUTOSOMAL RECESSIVE INHERITANCEThe recessive trait is expressed only in homozygous state. The homozygote receives one abnormal (recessive) gene from each parent. The trait appears only in sibs. The pedigree analysis of an autosomal recessive trait presents following features

CHARACTERISTICS OF AUTOSOMAL RECESSIVE INHERITANCE

1. An autosomal recessive phenotype, if it appears in more than one member of a kindred, typically is seen only in sibship of the proband not in parents, offsprings or other relatives.2. For most autosomal recessive diseases males and females are equally likely to be affected.3. Parents of an affected child are symptomatic carriers of mutant alleles.4. Parents of the affected person may in some cases be consanguineous. This is especially likely if the gene responsible for the condition is rare in the population.5. The recurrence risk for each sib of the affected proband is 1 in 4.

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