inheritance and Mendelian geneticsbiology 1

• Mendel provided the experimental basis for modern genetics– Law of Segregation– Law of independent assortment

• Use of probability in genetics

• Relationships between genotype and phenotype

• Some human genetic disorders

Pre-mendelian beliefs• Blending theory; traits blend like liquids,

heritable features become irreversibly inseparable– CON: individuals would eventually blend to a

uniform appearance between individuals– CON: traits would not be able to re-appear once

blended

• Thus the blending theory was replaced by the particulate theory of heredity in 1860s

Mendel• Particulate theory of heredity:

– Parents transmit to their offspring discrete inheritable factors (now called genes) that remain as separate factors from one generation to the next)

• Mendel demonstrated his theory by breeding pea plants with specific variants of trait contributing towards a character

Definitions of Mendelian experimentation• Parental (P) generation

• F1 generation - hybrid offspring of parental generation

• F2 generation - offspring resulting from self-pollination of F1

• True breeding: always produces plants with the same traits as parental generationr

• This experimentation resulted in Mendel Laws - the law of segregation, and the law of independent assortment

The Law of Segregation• Each trait corresponds to an allele.

When breeding, each allele is packaged into a gamete (ie., genes are not blended)– For example, true-breeding purple flower

crossed with true-breeding white flower results in all-purple flower F1

– When F1 is self-pollinated, white flower trait reappears in ratio of:

Purple:white = 3:1

• Mendel proposed that – Alternative forms of genes are responsible for variation

in inherited characters (eg., for flower color gene, two alleles - purple trait and white trait

– for each character, an organism inherits two alleles, one from each parent (eg., homologous chromosones)

– If the two alleles differ, one is fully expressed (dominant allele, denoted in upper case, eg., Purple = P), and one is completely masked (recessive allele, denoted in lower case, eg., white = p)

– The two alleles segregate during gamete production (meiosis), thus gametes of true-breeders will carry the same alleles to the offspring. BUT, if different alleles are present in the parent, then there is a 50:50 chance of which allele is passed on

• Thus Mendel’s Law of Segregation states that allele pairs from homologous chromosomes segregate during gamete formation (meiosis), and the paired condition is restored by the random fusion of gametes at fertilization– This law predicts a 3:1 ratio of phenotype in

the F2 of a monohybrid cross

– Simple mendelian problems such as this can be calculated using Punnett squares

More vocabulary• Homozygous - identical alleles in homologous

chromosomes (ie, PP, or pp) - such organisms are true-breeding

• Heterozygous - different alleles in homologous chromosomes (ie, Pp) - such organisms are not true-breeding

• Phenotype - an organism’s expressed traits• Genotype - an organism’s genetic makeup

The test-cross

• If some alleles are dominant over others, there may be no way to determine genotype from phenotype (e.g. PP vs Pp?)

• Use a test-cross to determine such questions– Cross unknown with homozygous recessive

• If unknown is Homozygous dominant, then offspring should all demonstrate dominant phenotype

• If unknown is heterozygous, the offspring should be 50:50 dominant trait to recessive trait

The Law of independent assortment• Each pair of alleles segregates into gametes

independently• To demonstrate this, consider the dihybrid cross (this

examines two characteristics simultaneously)• Mendel bred true breeding plants with yellow round

seeds (YYRR, gamete = YR) against green wrinkled seeds (yyrr, gamete = yr)– Dihybrid F1 is heterozygous for both traits (YyRr)

– Under two models• F2 progeny demonstrates non-independent assortment ratio of 3:1

• F2 progeny demonstrates independent assortment ratio of 9:3:3:1

Using probability in Mendelian genetics

• Segregation and random assortment are random events, and can thus be characterized by probability

• The two rules of probability state that:• The probability of an outcome ranges from 0 to 1• The probabilities of all possible outcomes for an

event sum to 1• The outcome of a random event is unaffected by

the outcome of previous events

• If you cross Pp with itself, what is the probability of pp?– For pp to occur, the two gametes that fuse must be p and p– Probability of a Pp plant giving rise to a p gamete is 0.5– Law of multiplication states that

p(pp) = p(p) x p(p) = 0.5 x 0.5 = 0.25

• In a dihybrid cross (YyRr x YyRr), what is the probability of YYRR?– For YYRR to occur, the two gametes that fuse must be YR

and YR– Probability of a YyRr plant giving rise to a YR gamete is 0.25– Law of multiplication states that

p(YYRR) = p(YR) x p(YR) = 0.25 x 0.25 = 0.0625

• Probability’s Law of addition can also be used:

• In a monohybrid cross of heterozygotes, what is the probability of a heterozygote offspring?

• Dominant sperm fuses with recessive egg:

p(P) x p(p) = 0.5 x 0.5 = 0.25• Recessive sperm fuses with dominant egg

p(p) x p(P) = 0.5 x 0.5 = 0.25

• p(Pp) = p(Pp) + p(pP) = 0.25 + 0.25 = 0.5

The relationship between genotype and phenotype

• Mendel was fortunate to select for his subject material a simple system

• Dominance does not imply abundance• Dominance relationships vary on a continuum from

– Complete dominance (AA and Aa have the same phenotype)

– Incomplete dominance (Aa is an intermediate phenotype)

– Codominance (Aa = both alleles expressed simultaneously)

Multiple Alleles• More than two alleles possible for a gene -

for example, blood; IA, IB, i

Blood type Possible

genotypes

Antigens on

red blood cell

Antibodies in

the serum

A IAIA

IAi

A Anti-B

B IBIB

IBi

B Anti-A

AB IAIB A, B -

O ii - Anti-A

Anti-B

Pleiotropy

• The ability of a single gene to have multiple phenotypic effects

• e.g., sickle cell anemia causes multiple symptoms, only one of which is the actual sickle celled condition

Epistasis• A condition in which a gene at one locus

can effect the phenotypic expression of a second gene

• Epistasis between two nonallelic genes causes deviation from the predicted 9:3:3:1 Mendelian ratio

• For example, in mice, fur color controlled by two genes - C (melanin deposition, and B (Black versus brown)

Polygenic inheritance• A mode of inheritance in which the additive effect of

two or more genes determines a single phenotypic character

• For example, skin pigmentation is controlled by at least 3 genes, A B and C– AABBCC results in darkest shade– aabbcc results in lightest shade

• Each gene contributes equally AaBbCc = AABbcc

• Environmental factors may also effect shade

Human Genetic Disorders• Recessive alleles that cause human disorders

are usually defective versions of normal alleles– Defective alleles usually code for a malfunctioning or

no protein at all (some heterozygote protection)• Recessive inherited traits range from nonlethal (albinism) to

lethal (cystic fibrosis)

• These traits are only active in the case of homozygous recessive

• Heterozygotes are carriers

• Cystic fibrosis occurs 1/2500 in caucasian populations. 4% of caucasians are carriers. Dominant allele codes for production of membrane protein that controls intake/outake of chloride. Homozygous recessive individuals unable to control chloride passage. Disease symptoms result form build up of fluid in lungs and pancreas

• Tay Sachs disease occurs 1/3600 (incidence is higher in a particular group of jewish people). Brain cells are unable to breakdown a vital lipid that interferes in the CNS. Accumulation of lipid causes seizures, blindness and deterioration of motor performance

• Sickle cell anemia effects 1/400 african-americans. Caused by a single amino acid substitution in hemoglobin. Sickle cells clog arteries. Approx. 1/10 african-americans are heterozygous carriers. Codominance of allele means heterozygotes can survive effects of disease (also helps battle malaria)

• Dominantly inherited disorders are rarer, since their presence cannot be hidden in a heterozygote– include Huntingdon’s disease, a

deterioration of the nervous system

• Multifactorial disorders are diseases that have both an environmental and genetic basis, including– Heart disease, diabetes, cancer,

alcoholism, and some forms of mental illness