Extending Mendelian Genetics

• Incomplete dominance• Codominance• Multiple alleles• Lethal alleles• Gene Interaction• Polygenic inheritance

or quantitative trait

• Pleiotropy• Effect of environment• Linkage• Sex-linked traits

Alleles and Symbols

• A – __________; a – ______________• + ; a+ - _________, a – mutant• Leu+, leu- ; leu+ is wild typeGene: Gal; galProtein coded:GAL1, GAL2, etc

Modifications of Dominant Relationships

Incomplete Dominance

• Snapdragons:AA - red; aa – whiteAa – pinkP: __________________F1: _________________

• Neither allele is dominant

Coat Color in Horses

CC – light chestnut (sorrel)CCcr – yellow or cream (palomino)CcrCcr – very light (cremello)

Plumage Color In Chicken

P: black x whiteF1: bluish grey (Andalusian blues)F2: 1 black : 3 blue : 1 whiteCB CB – black, ______________________CW CW – white CB CW – __________________________

Pigmentation in Birds and Mammals

• PIGMENTATION in birds and mammals is based on the synthesis of two different types of melanin, brown/black eumelanin and yellow/red pheomelanin.

• Tyrosinase is the rate-limiting enzyme of melanin biosynthesis, which takes place in melanosomes within melanocytes. Tyrosinase and the tyrosinase-related proteins Tyrp1 and Tyrp2 (Dct) are involved in the production of eumelanin.

• ________________ is associated with synthesis of eumelanin whereas _______________ results in the production of pheomelanin.

• The spherical pheomelanin premelanosomes are less organized than the rod-shaped eumelanin premelanosomes and contain less melanin

Intermediate Level of Gene Expression

• Tay-Sachs disease –fatal lipid-storage disorder (lipid accumulates in lysosomes in brain cells, eventually killing the brain cells)

• TT – _____________________________• tt – _______________________________• Tt - ?

Codominance

Heterozygote exhibits the phenotypes of both homozygotes

Codominance• Products of ______________________________; clearly detected for

biochemical phenotypes• Biochemical phenotype - a phenotype that is revealed by biochemical

experimentation; examples are – DNA markers (RFLPs); – protein markers (isozymes); – quantity of a metabolite; – immunological reaction

• MN blood group; autosomal locus, Chr4– Glycoprotein M; glycoprotein N– _____________________________________

Codominance

Genotypes can also be assigned to DNA fragments •A1 = 3.0 kb fragment; A2 = 2.0 kb fragment •Parent 1 = A1A1 •Parent 2 = A2A2. •F1 = A1A2 (heterozygous). •F2 generation will segregate 1 A1A1:2 A1A2:1 A2A2

Multiple Alleles

Can be more than two variants of a gene Each diploid organism can only have two alleles present

Multiple alleles: white Locus in Drosophila

• The recessive eye mutation• Discovered by Thomas Morgan and Calvin

Bridges in 1912• More than 100 alleles: allelic series• Red w+>wa>we>wt > w, white

Test for Allelism: Complementation Analysis

• To find if a mutation is coded by an allele of a gene or by another gene:– Cross with

____________________________________– If F1 is wild type – _____________________– If F1 is mutant phenotype –

__________________________________

Coat Color In Rabbits

• cc – white over the entire body or albino• chch – himalayan, black hair on extremities• cchcch – chinchilla,white hair with black tips• c+c+ - wild type, colored hair• c for

________________________________

Coat Color In Rabbits

• c+ > cch >ch > ca;

• P: c+cch x cchca full color x himalayan

c+ cch

cch

ca

Multiple Alleles – Blood Groups

• There are four different blood groups: O, A, B, AB

• The ABO Blood group alleles: IA, IB, IO or i• Genotypes:

Antigens

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

ABO Blood Groups: biochemical basis

• Cell membrane proteins, _________________• H substance plus fucose plus one more sugar added

(galactose or N-acetylgalactosamine)• IA codes for enzyme (glycosyltransferase) responsible

for adding N-acetylgalactosamine (AcGALNH) – ____________________

• IB codes for enzyme that can add galactose, but not AcGALNH – ____________________

• Allele i – no enzymes, no added sugars• IAIB -?

ABO Blood Groups: biochemical basis

The Bombay Phenotype

• A x AB parents• Woman O• Children AB, A, B

The Bombay Phenotype

• Genetically B, functionally O• Homozygous for fut1/fut1 – no

fucosyltransferase, ________________________________

• Not recognised by glycosyltransferase, no sugar added, ____________________

• Actually two genes system

ABO blood groups and paternity testing

• For example, child with blood type O must be genotype i/i.

• The parents could be___________ • However, they could not be__________ • May be used to suggest paternity,

additional analyses are often needed

Lethal Alleles

Determine conditions that are lethal, usually in homozygous state

Lethal Alleles

• 1904, Lucien Cuenot – color of mice– Yellow mice x wild type ; F1 1:1– Yellow mice x yellow mice– F1 – ___________________________

Lethal Alleles• Loss of function – can survive as Aa, but

not aa – homozygous recessive lethal• In mice:AA – agouti; AAY – yellow• AAY x AAY

A AY

A

AY

Figure 4-4 Copyright © 2006 Pearson Prentice Hall, Inc.

Why Some Alleles Are Dominant and Some Recessive?

• Abnormal protein leads to abnormal cell form and function – _________________________

• Other mutations may lead to – gain of function; – inhibit, antagonize or limit activity of wild-type

allele

Yellow Coat Color In Mice – Molecular Analysis

Merc gene coding region Regulatory coding region

A gene (Agouti)

Deletion (AY)

Merc – critical in embryonic development

Manx Mutation In Cats

Dominant Lethal Genes

• Spontaneous dominant mutation– normal height – _________________– Dwarfs – _______________________– AA – _____________________________– affects less than 200,000 people in the US

population

Huntington Disease

• Chromosome 4• Mutation of the gene causes Huntington

chorea, dominant, ____________________________ (1:10,000)

• _________ of the gene – Wolf-Hirschhorn syndrome, carriers die young

Pleiotropy

Multiple effects of one gene

Pleiotropy

• One gene – multiple phenotypic effects– Sickle cell anemia –

• ________________________________________– Marfan syndrome

Marfan Syndrome

• Marfan's syndrome is a genetic (inherited) disorder that affects the body's connective tissue.

• Connective tissue is the tough, fibrous, elastic tissue that connects one part of the body with another. It is a major part of tendons, ligaments, bones, cartilage and the walls of large blood vessels.

• In Marfan's syndrome, the body can't produce enough _____________ an important building block of connective tissue

Marfan Syndrome

• The problem in Marfan's syndrome is caused by a _______________________.

• In many families with inherited Marfan's syndrome, the mutation affects the FBN1 gene on ________________, although a second gene on chromosome 5 may be involved in some cases.

Sickle Cell Anemia

• Disease caused by __________________________ in the sequence of DNA coding a hemoglobin protein

• Leads to – ____________________________– Abnormal cell form– Abnormal RBC function