Mendelian inheritance of disease, Monogenic vs Polygenic diseases

Genetics

Study of heredity and heritable information

Genotype

Genetic constitution of an individual

Phenotype

Observable physiological and physical characteristics of an organism

Gene

Unit of hereditary information controlling a specific trait

Allele

Alternative version of the same gene

Who is the father of modern genetics?

Gregor Mendel

What organism did Mendel use in his experiments?

Pea plants

True breeding

Plants that produce offspring of the same variety upon self-pollination

What did Mendel conclude causes alternative phenotypes?

Different inherited factors now known as genes

What are different forms of a gene called?

Alleles

How many alleles does a diploid individual possess for a gene?

Two alleles

Dominant allele

Allele expressed in the phenotype when present

Recessive allele

Allele masked by a dominant allele in a heterozygote

Law of Segregation

The two alleles of a gene separate during gamete formation so each gamete receives one allele

What process explains the Law of Segregation?

Separation of alleles during meiosis

Monohybrid cross phenotypic ratio

3:1

Monohybrid cross genotypic ratio

1:2:1

Law of Independent Assortment

Alleles of different genes assort independently during gamete formation

What ratio is produced by a dihybrid cross?

9:3:3:1

What is the phenotypic ratio of double dominant:single dominant:double recessive in a dihybrid cross?

9:3:3:1

What does independent assortment apply to?

Different pairs of alleles controlling different traits

Exception to Mendelian inheritance

Codominance

Exception to Mendelian inheritance

Incomplete dominance

Exception to Mendelian inheritance

Multiple alleles

Exception to Mendelian inheritance

Linkage

Exception to Mendelian inheritance

Mitochondrial inheritance

Codominance

Both alleles are fully expressed in the heterozygote

Example of codominance

MN blood group

MN blood group heterozygous genotype

LMLN

Phenotype of LMLN genotype

Expresses both M and N antigens

Codominance F2 phenotypic ratio

1:2:1

Incomplete dominance

Heterozygote shows an intermediate phenotype between homozygotes

Why does incomplete dominance occur?

Reduced gene product compared with complete dominance

Incomplete dominance heterozygote phenotype

Intermediate between dominant and recessive phenotypes

Multiple alleles

More than two alleles exist for a gene in a population

How many alleles can a diploid individual possess despite multiple alleles existing?

Only two alleles

Example of multiple alleles

ABO blood group system

ABO blood group major alleles

A, B, and O

How many phenotypes are found in ABO blood grouping?

Four phenotypes

Patterns of inheritance

Autosomal, sex-linked, mitochondrial, and polygenic/multifactorial

Autosomal inheritance

Inheritance of genes located on non-sex chromosomes

Autosomal dominant inheritance

Disease is expressed when one mutant allele is present

Autosomal recessive inheritance

Disease is expressed only when two mutant alleles are present

Key feature of autosomal dominant inheritance

Every affected individual usually has an affected parent

Can unaffected individuals transmit autosomal dominant diseases?

No

Autosomal dominant affected to unaffected offspring ratio

Approximately 1:1

Sex distribution in autosomal dominant inheritance

Males and females equally affected

Can autosomal dominant traits be transmitted from father to son?

Yes

Pedigree clue for autosomal dominant inheritance

Vertical transmission through generations

Brachydactyly inheritance pattern

Autosomal dominant

Marfan syndrome inheritance pattern

Autosomal dominant

Huntington disease inheritance pattern

Autosomal dominant

Marfan syndrome characteristic features

Tall stature, slender body, long fingers

Huntington disease

Progressive neurodegenerative disorder causing CNS deterioration

Key feature of autosomal recessive inheritance

Affected children may be born to unaffected parents

Sex distribution in autosomal recessive inheritance

Males and females equally affected

What happens if both autosomal recessive parents are affected?

All offspring are affected

Affected autosomal recessive individual with normal partner usually has

Normal children

Pedigree clue for autosomal recessive inheritance

Trait often skips generations

Albinism inheritance pattern

Autosomal recessive

Cystic fibrosis inheritance pattern

Autosomal recessive

Tay-Sachs disease inheritance pattern

Autosomal recessive

Albinism defect

Failure to convert tyrosine into melanin precursor

Characteristic features of albinism

Very pale skin and hair with light-colored eyes

Cystic fibrosis basic defect

Abnormal chloride ion transport

Organs commonly affected in cystic fibrosis

Lungs and pancreas

Tay-Sachs disease enzyme deficiency

Hexosaminidase A deficiency

Tay-Sachs disease major system affected

Nervous system

Sex-linked inheritance

Inheritance of genes located on sex chromosomes

Most common type of sex-linked inheritance

X-linked recessive

X-linked recessive trait expression in females

Usually only homozygous females are affected

Heterozygous female in X-linked recessive inheritance

Carrier

Hemizygous

Having only one copy of a gene, as in males for X-linked genes

Why are males commonly affected by X-linked recessive disorders?

They possess only one X chromosome

Can fathers pass X-linked recessive disorders to sons?

No

Haemophilia inheritance pattern

X-linked recessive

Colour blindness inheritance pattern

X-linked recessive

Duchenne muscular dystrophy inheritance pattern

X-linked recessive

Haemophilia A defect

Factor VIII deficiency

Red-green colour blindness cause

Absence or deficiency of red or green cone function

Duchenne muscular dystrophy cause

Mutation in the dystrophin gene

Y-linked inheritance

Inheritance of genes located on the Y chromosome

Who is affected in Y-linked inheritance?

Only males

How are Y-linked traits transmitted?

Affected father to all sons

Can daughters inherit Y-linked traits?

No

Example of a Y-linked gene

Testis-determining factor (SRY)

Y chromosome infertility

Y-linked disorder causing impaired sperm production

XYY syndrome

Presence of an extra Y chromosome causing tall stature and learning difficulties

46,XX testicular disorder of sex development

Male phenotype despite two X chromosomes due to SRY translocation

Mitochondrial inheritance

Inheritance of mutations in mitochondrial DNA through the maternal line

Why is mitochondrial inheritance maternal?

Zygote receives functional mitochondria from the oocyte

Can affected fathers transmit mitochondrial diseases?

No

Can affected mothers transmit mitochondrial diseases?

Yes, to all children

Sex distribution in mitochondrial disorders

Males and females equally affected

MELAS

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes

Leber hereditary optic neuropathy

Maternal mitochondrial disorder causing central vision loss

Most human diseases are caused by

Interaction of genetic and environmental factors

Down syndrome is an example where

Genetic factors predominate

Infectious diseases are examples where

Environmental factors predominate

Multifactorial inheritance

Disease caused by combined genetic and environmental factors