Non-Mendelian Genetics

Concepts Mendel Didn’t Think About

Alleles Alter Phenotypes in Different

Ways• Alternative forms of a gene are called alleles.

•Mutation is the source of alleles.

•The wild-type allele is the one that occurs most frequently in nature and is usually, but not always, dominant.

Mutations

• Often, a mutation causes the reduction or loss of the specific wild-type function.

• Such a case is called a loss of function mutation. – Not being able to grow without the outside

addition of an amino acid (adenine)

• If the loss is complete, the mutation has resulted in what is called a null allele.

• Some mutations may enhance the function of the wild type product = gain of function mutation

•Silent mutation = Mutation where no phenotypic change is detected but there is a change in the DNA sequence

•Phenotypic traits may be influenced by more than one gene and the allelic forms of each gene involved.

Symbols for Alleles• Dominant alleles are usually indicated either by an italic uppercase letter (D) or by a an italic letter or group of letters followed by a superscript + (Wr+).

•Recessive alleles are usually indicated either by an italic lowercase letter (d) or by an italic letter or group of letters (Wr) without the +.

•If no dominance exists, italic uppercase letters and superscripts are used to denote alternative alleles (R1, R2; CW, CR).

Incomplete Dominance

• Neither allele is dominant• Heterozygotes are a blend

of homozygous phenotypes = no distinct expression of either allele

• F2 phenotypic and genotypic ratios are 1:2:1

• Snapdragon/Four o’clock flower color

• Eggplant color• Tay-Sachs disease

Try these

• In a plant species, if the B allele (blue flowers) and the b allele (white flowers) are incompletely dominant (Bb is light blue), what offspring ratio is expected in a cross between a blue-flowered plant and a white-flowered plant?

• What would be the phenotypic ratio of the flowers produced by a cross between two light blue flowers?

Codominance

• Both alleles are equally dominant

• Heterozygotes express both alleles = distinct expression of the gene products of both alleles can be detected

• MN blood group• F2 genotype and

phenotype ratios are 1:2:1

Genotype Phenotype

LMLM M

LMLN MN

LNLN N

Try These1. Cattle can be red (RR = all red hairs), white

(WW = all white hairs), or roan (RW = red & white hairs together.

a. Predict the phenotypic ratios of offspring when a homozygous white cow is crossed with a roan bull.

b. What should the genotypes & phenotypes for parent cattle be if a farmer wanted only cattle with red fur?

2. A cross between a black cat & a tan cat produces a tabby pattern (black & tan fur together).

a. What pattern of inheritance does this illustrate? b. What percent of kittens would have tan fur if a

tabby cat is crossed with a black cat?

Multiple Alleles

• Genes can be characterized by more than 2 alleles

• Multiple alleles (>2) can be studied only in populations, because any individual carries only 2 alleles at a particular locus at one time

• ABO blood groups – Each individual is A, B, AB, or O phenotype – Phenotype controlled by isoagglutinogen marker on

RBC– IA and IB alleles are dominant to the IO allele – IA and IB alleles are codominant to each other

• The IA allele is responsible for an enzyme that can add the terminal sugar N-acetylgalactosamine (AcGalNH) to the H substance.

• The IB allele is responsible for a modified enzyme that cannot add N-acetylgalactosamine but instead can add a terminal galactose.

• The O phenotype results from an absence of either terminal sugar

PhenotypePossible Genotype

Antigen on RBC surface

Antibody Made in Plasma

Can Donate

To

Can Receive

From

A IAIO, IAIA A Anti-B A, AB A, O

B IBIO,IBIB B Anti-A B, AB B, O

AB IAIB AB Neither ABA, B, AB, O

O IOIO O BothA, B, AB, O O

Try These1. If a male has blood type B and a female

has blood type A, what are the possible blood types in the offspring?

2. Is it possible for a child with Type O blood to be born to a mother who is type AB? Why or why not?

3. A child is type AB. His biological mother is also type AB. What are the possible phenotypes of his biological father?

X-Linkage/ Sex Linked

• Genes are located on the X chromosome

• Drosophila eye color was one of the first examples of X-linkage described

• Discovered in 1910 by Thomas Hunt Morgan

X-Linked/Sex Linkage

• Genes present on the X chromosome exhibit unique patterns of inheritance due to the presence of only one X chromosome in males.– Males are referred to as hemizygous

• X-linked disorders show up rarely in females

• X linked disorders show up in males whose mothers were carriers (heterozygotes)

Y-linked Inheritance• Y chromosome contains only 70-300 genes

although it is 50million base pairs in length.

• Most of Y is junk DNA

• Genes on Y are not essential for survival

• Passed strictly from father to son

• Most Y-linked traits are related to male sexual function and fertility

• Exception = Hairy Ears

Pedigree Analysis

• Method of tracking a trait through generations within a family.

• Good method of tracking sex-linked traits as well as autosomal traits.

Sex-Linked Pedigree

• Shows gender bias with males exhibiting the trait more often than females

Autosomal Dominant Pedigree

• Autosomal dominant traits do not skip a generation

• Autosomal dominant traits do not show gender bias

Autosomal Recessive Pedigree

• Autosomal recessive traits skip a generation

• Autosomal recessive traits do not show gender bias

Lethal Alleles• A loss of function mutation can sometimes be

tolerated in the heterozygous state but may behave as a recessive lethal allele in the homozygous state, in which case homozygous recessive individuals will not survive.

• The allele responsible for a lethal effect when it is homozygous can also result in a distinctive mutant phenotype when it is heterozygous. Such an allele is behaving as a recessive lethal, but is dominant with respect to the phenotype

• Will produce a 1:2 phenotypic and genotypic ratio

Lethal Allele Exception

• Huntington’s Disease– Inherited as an autosomal

dominant lethal disorder– Persons with Huntington’s will

develop a progressive nerve disorder that causes involuntary muscle movement and loss of mental function

– Huntington’s is usually expressed in adulthood and is always fatal

Try This

• A cross between two short-tailed mice results in offspring in the ratio of 2/3 short-tailed and 1/3 long-tailed. What is the best explanation for this result?

Modifying the Dihybrid Ratio

• Combinations of two gene pairs involving two modes of inheritance modify the 9:3:3:1 ratio– Mendel’s principle of independent

assortment applies to situations in which two modes of inheritance occur simultaneously, provided that the genes controlling each character are not linked on the same chromosome.

– The probability of each phenotype arising in a cross can be determined by the forked-line method or by Punnett square assuming that the genes under consideration undergo independent assortment.

Epistasis

• Occurs when one gene masks the effect of another gene or when two gene pairs complement each other such that one dominant allele is required at each locus to express a certain phenotype.

• When studying a single characteristic, a ratio expressed in 16 parts (e.g., 3:6:3:4) suggests that epistasis is occurring.

Recessive Epistasis

• Occurs when the homozygous recessive genotype masks or suppresses expression of another gene

• The Bombay phenotype for ABO blood groups

Dominant Epistasis

• Dominant allele at one genetic locus masks the expression of the alleles of a second locus

• Summer squash color

Complementary Gene Interaction

• A form of epistasis

• Presence of at least one dominant allele in each gene pair is essential to produce a particular phenotype– Each gene enhances the other

• Sweet Pea Flower Color

Novel Phenotypes

• In addition to modifying the dihybrid ratio, gene interaction may introduce new phenotypes which will be observed among heterozygotes

• Squash fruit shape

Pleiotropy

• Expression of a single gene has multiple phenotypic effects

• Very common among human genetic disorders

• Marfan Syndrome

• Porphyria variegata

Penetrance• Penetrance = probability that an

individual having the dominant allele will show the associated phenotype– Complete– Incomplete

• Polydactyly

– Reported as a percentage

Expressivity• Expressivity = The degree to which an

allele expresses the phenotype (i.e. the strength of the trait)– Variable among individuals

• Affected by various factors– Genetic background (suppression and position of

genes)– Temperature

• Himalayan rabbits

– Nutrition• PKU• Lactose Intolerance

• Onset of gene expression may differ among individuals

• TaySachs, Huntingtons Disease

Expressivity -- Genomic Anticipation

• Trait seems to grow stronger and gain more expressivity from one generation to the next

• Ex: Schizophrenia, Huntington’s Disease

• Why?– During DNA replication repeated sections of

the DNA within the gene are over-duplicated by accident

– In successive generations the gene gets longer

Genomic Imprinting

• Gender of the parent who contributes the allele may affect how the trait is expressed

• Ex: Solid Gold (sheep)

• Why?– Unclear and seems to vary for different

genes– Becoming an issue with cloning