EXTENSIONS OF MENDELIAN GENETICS

What happens when inheritance doesn’t follow the patterns observed by Mendel? There are many reasons why traits might deviate from expected.

Alleles Alter Phenotypes in Different Ways Main Concepts Alleles Alter Phenotypes in Different Ways Incomplete Dominance Codominance Multiple Alleles Lethal Alleles Phenotypes Often Affected by More Than One Gene (Polygenic) A Single Gene May Have Multiple Effects (Pleiotropy) Sex Linked Traits Sex-Limited and Sex-Influenced Inheritance

Different types of mutations can alter alleles (or produce new ones) How are alleles formed? MUTATION Wild-type allele: occurs most frequently in nature and is usually dominant Different types of mutations can alter alleles (or produce new ones)

Mutations Loss of function mutation: a mutation that causes the reduction/loss of the specific wild-type function If the loss is complete, the mutation has resulted in what is called a null allele Gain of function mutation: a mutation that enhances the function of the wild-type allele

Incomplete Dominance Incomplete dominance – heterozygotes show a distinct intermediate phenotype different from homozygous genotypes Neither trait is dominant

Symbols Alleles that are incompletely dominant are written using a superscript letter. Flower color: CWCW (white) plant X CRCR (red) plant will produce all CRCW offspring

Are these traits blended? NO … the alleles are particulate (they remain separate and do not influence each other). How do we know? A cross of two pink individuals will produce red, white and pink individuals. The phenotypic ratio will be 1:2:1, like the genotypic ratio

Figure 4-1 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 4-1 Incomplete dominance shown in the flower color of snapdragons. Figure 4-1 Copyright © 2006 Pearson Prentice Hall, Inc.

Incomplete Dominance

What is really going on? White allele is most likely a “loss of function” mutation Wild type (red) “codes” for synthesis of red pigment Mutant allele (white) cannot synthesize the pigment Therefore, the heterozygote only produces ½ the amount of pigment (pink)

True incomplete dominance is rare Individuals may appear completely dominant until viewed at the molecular level Tay-Sachs disease Homozygous recessive = severely affected, death before age 3 Heterozygotes appear normal, but only produce about 50% of normal enzymes Threshold effect

The threshold effect - normal phenotypic expression occurs whenever a certain level (≤ 50%) of gene product is attained.

Codominance Codominance – 2 alleles affect the phenotype in separate, distinguishable ways Alleles for curly hair and straight hair are codominant Curly hair = homozygous for curly hair alleles Straight hair = homozygous for straight hair alleles Heterozygous individuals have wavy hair

Incomplete Dominance vs. Codominance With incomplete dominance we get a reduced function of the dominant trait (due to recessive), so that the third phenotype is something in the middle (red x white = pink). In codominance, the "recessive" & "dominant" traits appear together in the phenotype of hybrid organisms – appears to be a “blend”

Dominance = common? Polydactyly – an allele that is dominant to the recessive allele for 5 digits Recessive allele more common – 99% have 5 digits

Multiple Alleles Can only be studied in populations WHY? Because individuals can only have 2 alleles for a gene! Example of trait covered by multiple alleles? Human Blood Type ABO antigens

I stands for “isoagglutinogen”, which is another word for antigen. ABO blood groups in humans are determined by three alleles, IA, IB, and IO (also referred to as i) Both the IA and IB alleles are dominant to the IO allele The IA and IB alleles are codominant to each other I stands for “isoagglutinogen”, which is another word for antigen.

How many blood types are possible? Because each individual carries two alleles, there are six possible genotypes and four possible blood types IA IA or IAIO- type A IB IB or IBIO- type B IA IB - type AB IOIO - type O

Table 4-1 Copyright © 2006 Pearson Prentice Hall, Inc. Table 4.1 Potential Phenotypes in the Offspring of Parents with All Possible ABO Blood Group Combinations, Assuming Heterozygosity Whenever Possible Table 4-1 Copyright © 2006 Pearson Prentice Hall, Inc.

The blood types differ due to the molecules that are present on the outside of RBC (antigens)

Lethal Alleles Loss of function mutation Can (sometimes) be tolerated in heterozygous state Can have a mutant phenotype (acts dominant) when heterozygous BUT… may be lethal in the homozygous state

Figure 4-4 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 4-4 Inheritance patterns in three crosses involving the normal wild-type agouti allele (A) and the mutant yellow allele in the mouse. Note that the mutant allele behaves dominantly to the normal allele in controlling coat color, but it also behaves as a homozygous recessive lethal allele. The genotype does not survive. Figure 4-4 Copyright © 2006 Pearson Prentice Hall, Inc.

Lethal alleles In some cases, the lethal allele is DOMINANT, so even heterozygotes will die. Why does this allele persist in the population? Late acting (Huntington’s) Individuals reproduce before allele takes affect

Polygenic Traits Many traits with a distinct phenotype are affected by more than one gene The cellular function of numerous gene products contributes to the development of a common phenotype Ex - skin color in humans is controlled by at least 3 different genes

AABBCC (dark) and aabbcc (light) Imagine - each gene has 2 alleles, (light/dark), demonstrate incomplete dominance AABBCC (dark) and aabbcc (light) Cross between 2 AaBbCc (intermediate) produces wide range of shades

Epistasis Epistasis - a gene at one locus alters the phenotypic expression of a gene at a second locus One gene can mask the effect of the other gene Two gene pairs can complement each other, such that one dominant allele is required at each locus to express a certain phenotype

Epistasis example Mice (and many other mammals) - coat color depends on two genes One (epistatic gene), determines whether pigment will be deposited in hair Presence (C) is dominant to absence (c) Second determines whether pigment deposited is black (B) or brown (b) The black allele is dominant to the brown allele Individual with cc has a white (albino) coat regardless of the genotype of the 2nd gene

Epistasis – more complex In cats (and other mammals), a pattern of hair termed “agouti” is an example of epistasis Some cats have hairs in which there is more than one color distributed along the hair shaft (banded – agouti) Agouti fur color is typical of many wild animals such as mice squirrels and rabbits – good for camouflage!

Agouti is determined by the dominant agouti allele, A Hairs on non-agouti cats are unbanded, producing a solidly colored coat Such a cat is homozygous for the non-agouti allele (aa) at the agouti locus Again – regardless of color. SO … you could have an agouti brown, agouti black, etc.

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

Pleiotropy Pleiotropy occurs when expression of a single gene has multiple phenotypic effects, and it is quite common For example, the wide-ranging symptoms of sickle-cell disease are due to a single gene

Marfan syndrome What US president may have had Marfan?

The Environment Phenotype is not always a direct expression of genotype The environment plays a role in a gene’s expression.

Environmental Mutations Conditional or temperature-sensitive mutations - mutations affected by temperature useful in studying mutations that affect essential processes Nutritional mutations – mutations affected by diet may prevent phenotype from reflecting genotype. Ex -mutations in a biosynthetic pathway

X-linked or Sex linked traits Genes are located on the X chromosome Present a unique pattern of inheritance due to the presence of only one X chromosome in males Females (XX) can be heterozygous (carriers), while their sons (XY) can express the disease/trait.

Drosophila (fruit fly) eye color was one of the first examples of X-linkage described Drosophila was a favorite model organism for Thomas Hunt Morgan Morgan studied eye color in fruit flies – the trait did not have normal Mendelian ratios

Crosses between F1 produced classic 3:1 ratio Crosses of white-eyed male with a red-eyed female - all F1 offspring had red eyes The red allele appeared dominant Crosses between F1 produced classic 3:1 ratio Surprisingly, the white-eyed trait appeared only in males All the females and half the males had red eyes Morgan concluded that a fly’s eye color was linked to its sex

Figure 4-11 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 4-11 The F1 and F2 results of T. H. Morgan’s reciprocal crosses involving the X-linked white mutation in Drosophila melanogaster. The actual data are shown in parentheses. The photographs show white eye and the brick-red wild-type eye color. Figure 4-11 Copyright © 2006 Pearson Prentice Hall, Inc.

Figure 4-12 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 4-12 The chromosomal explanation of the results of the X-linked crosses shown in Figure 4–11. Figure 4-12 Copyright © 2006 Pearson Prentice Hall, Inc.

Table 4-3 Copyright © 2006 Pearson Prentice Hall, Inc. Table 4.3 Human X-Linked Traits Table 4-3 Copyright © 2006 Pearson Prentice Hall, Inc.

Lethal X-linked recessive disorders are observed only in males, since females can only be heterozygous carriers that do not develop the disorders.