Mendel's Laws of Inheritance

Gregor Mendel

• The blending concept of inheritance suggests that offspring have an intermediate appearance, contrasting parental traits
• Mendel formulated the particulate theory of inheritance
• Mendel proposed the laws of segregation and independent assortment
• Inheritance involves reshuffling of genes from generation to generation

Gregor Mendel's Background

• Mendel, an Austrian monk, studied science and mathematics at the University of Vienna
• Mendel conducted breeding experiments on the garden pea, Pisum sativum
• Experiments on the inheritance of simple traits disproved the blending hypothesis

Why the garden pea?

• Easy to cultivate
• Short generation
• Normally self-pollinating, but can be cross-pollinated by hand
• Pollen was transferred from the male (anther) of one plant to the female (stigma) parts of another plant
• True-breeding varieties available
• Simple, objective traits

Mendel's Laws

• Mendel performed cross-pollination experiments using true-breeding (homozygous) plants
• He chose varieties that differed in only one trait (monohybrid cross)
• Performed reciprocal crosses
• Parental generation = P
• First filial generation offspring = F₁
• Second filial generation offspring = F₂
• Formulated the law of segregation

Law of Segregation

• Each individual has a pair of factors (alleles) for each trait
• The factors (alleles) segregate (separate) during gamete (sperm and egg) formation
• Each gamete contains only one factor (allele) from each pair of factors
• Fertilization gives the offspring two factors for each trait

Mendel's Cross as Viewed by Modern Genetics

• Each trait in a pea plant is controlled by two alleles (alternate forms of a gene)
• Dominant allele (capital letter) masks the expression of the recessive allele (lowercase)
• Alleles occur on a homologous pair of chromosomes at a particular gene locus
• Homozygous = identical alleles
• Heterozygous = different alleles

Mendel's Law of Independent Assortment

• A dihybrid cross uses true-breeding plants differing in two traits
• Mendel tracked each trait through two generations
• It started with true-breeding plants differing in two traits
• The plants showed both dominant characteristics
• Plants self-pollinated
• He observed phenotypes among plants
• Mendel formulated the law of independent assortment
• The pair of factors for one trait segregate independently of the factors for other traits
• All possible combinations of factors can occur in the gametes

Mendel and the Laws of Probability

• Allows for easy calculation of probability of genotypes and phenotypes among the offspring
• Punnett square shown has 50% chance
• Chance of A = 1/2 and chance of a = 1/2
• The chance of AA = 1/2 x 1/2 = 1/4
• The chance of Aa = 1/2 x 1/2 = 1/4
• The chance of aA = 1/2 x 1/2 = 1/4
• The chance of aa = 1/2 x 1/2 = 1/4
• The sum rule allows to add the genotypes that produce the identical phenotype to find out the chance of a particular phenotype

Testcrosses

• Individuals with recessive phenotype always have the homozygous recessive genotype
• Individuals with dominant phenotype have indeterminate genotype
• May be homozygous dominant TT, or heterozygous Tt
• A testcross determines the genotype of an individual having the dominant phenotype

Mendelian Patterns of Inheritance and Human Disease

• Genetic disorders are medical conditions caused by alleles inherited from parents
• Autosome is any chromosome other than a sex chromosome (X or Y)
• Genetic disorders caused by genes on autosomes are called autosomal disorders
• An individual with AA or Aa has the disorder with autosomal dominant genetic disorders
• An individual with aa does NOT have the disorder with autosomal dominant genetic disorders
• An individual with AA or Aa does NOT have the disorder with autosomal recessive genetic disorders
• Aa is a carrier with autosomal recessive genetic disorders
• An individual with aa DOES have the disorder with autosomal recessive genetic disorders

Autosomal Recessive Disorders

• If both parents carry one copy of a recessive gene, they are unaffected but capable of having a child with two copies of the gene affected
• Methemoglobinemia is a relatively harmless disorder with skin appearing bluish-purple due to accumulation of methemoglobin in the blood
• Cystic Fibrosis causes mucus in bronchial tubes and pancreatic ducts to be particularly thick and viscous

Autosomal Dominant Disorders

• Two parents with a dominantly inherited disorder are affected when carrying one copy of the gene

Osteogenesis Imperfecta

• Characterized by weakened, brittle bones
• Most cases are caused by mutation in genes required for the synthesis of type I collagen

Huntington Disease

• Neurological disease that leads to progressive degeneration of brain cells
• Caused by mutated copy of the gene for a protein called huntingtin

Hereditary Spherocytosis

• Caused by a mutation in the ankyrin-1 gene.
• Red blood cells become spherical, fragile, and burst easily.

Beyond Mendelian Inheritance

• Some traits are controlled by multiple alleles
• The gene exists in several allelic forms, but each individual only has two alleles
• ABO blood types are an example
• The alleles are antigen on red blood cells/anti-B antibody in plasma; antigen on red blood cells/anti-A antibody in plasma; and neither A nor B antigens on red blood cells, both anti-A and anti-B antibodies in plasma
• The ABO blood type is also an example of codominance where More than one allele is fully expressed and both are expressed in the presence of the other

Incomplete Dominance

• Heterozygote has a phenotype intermediate between that of either homozygote
• Homozygous red has red phenotype
• Homozygous white has white phenotype
• Heterozygote has pink (intermediate) phenotype
• Phenotype reveals genotype without a testcross

Familial Hypercholesterolemia (FH)

• Homozygotes for the mutant allele develop fatty deposits in the skin and tendons and may have heart attacks during childhood
• Heterozygotes may suffer heart attacks during early adulthood.
• Homozygotes for the normal allele do not have the disorder

Pleiotropic Effects

• Pleiotropy occurs when a single mutant gene affects two or more distinct and seemingly unrelated traits
• Marfan syndrome has been linked to a mutated gene FBN1 on chromosome 15, coding for the fibrillin protein
• Marfan syndrome results in phenotypes like disproportionately long arms/legs/hands/feet, a weakened aorta, and poor eyesight

Polygenic Inheritance

• Occurs when a trait is governed by two or more sets of alleles
• Each dominant allele has a quantitative effect on the phenotype where these effects are additive
• It results in continuous variation of phenotypes within a population and traits may be affected by the environment
• Examples include human skin color, height, and eye color

Multifactorial Inheritance

• Multifactorial traits are controlled by polygenes & subject to environmental influences
• Examples include: Temperature, human skin and height
• For Himalayan rabbit, enzyme encoded by the gene involved in producing melanin is active only at low temperature so black fur occurs at the extremity, where heat is lost

X-Linked Inheritance

• The term X-linked is used for genes that have nothing to do with gender
• X-linked genes are carried on the X chromosome
• The Y chromosome does not carry these genes
• Most sex-linked experiments are performed on fruit flies
• They can be easily and inexpensively raised in simple laboratory glassware
• Fruit flies have a similar sex chromosome pattern to humans
• Morgan's experiments with X-linked genes apply directly to humans

Human X-Linked Disorders

Color Blindness

• The allele for the blue-sensitive protein is autosomal
• The alleles for the red- and green-sensitive pigments are on the X chromosome

Muscular Dystrophy

• Causes wasting away of the muscle
• It is caused by the absence of the muscle protein dystrophin

Hemophilia

• Absence or minimal presence of clotting factor VIII or clotting factor IX
• An affected person's blood either does not clot or clots very slowly