Exam 1: Lesson 5 - Transmission Genetics 1 (Mendelian Inheritance)

Who discovered the basis for transmission of hereditary traits?

Gregor Mendel

Why was the pea plant a good choice as a model organism for Mendel’s studies?

easy to cultivate, grows quickly, naturally self-fertilizes, and exhibits distinct, contrasting traits

For a monohybrid cross that starts with pure homozygous parents, what is the result of F1, F2?

F1= all dominant phenotype

F2= 3:1 dominant:recessive phenotype… but 1:2:1 genotype

What are Mendels 4 postulates? In modern terminology

a. Unit factors are in pairs= genes exist in pairs and control genetic characters

b. Dominance/ recessiveness= there is a dominant allele and a recessive allele

c. Random segregation= random segregation of paternal and maternal homologs in meiosis 1 anaphase

d. Independent assortment= non-homologous chromosomes assort independently from one another in meiosis 1 (homologs pair up while non-homologous chr do not affect each other)

What is a test cross?

Unknown genotype that expresses dominant phenotype is crosses with a homozygous recessive individual

—> if result is ALL dominant, then the unknown is homozygous dominant (DD)

—> if result is ½ dominant and ½ recessive, then the unknown is heterozygous dominant (Dd)

Do the test cross practice problem + draw forked line method

TtRRYy

How can a geneticist determine with one cross the genotype of an individual with a dominant

phenotype? Give one example.

Test Crossing! Cross an unknown genotype that has a dominant phenotype with a recessive genotype/phenotype (rr)… Ratios will tell you what the genotype of each phenotype is

• If 1:1 ratio between dom and rec, then unknown is heteozygote (Rr)

• If 1:0 ratio dom:rec, then unknown is homozygous dom (RR)

• If 0:1 ratio dom:rec, then unknown is homozygous rec (rr)

What is the ideal phenotypic ratio of the F2 generation in a dihybrid cross? (cross btwn 2 heteozygous GgWw x GgWw)

9:3:3:1

What are the conditions that must occur for the 9:3:3:1 ratio of F2 dihybrid cross to exist?

1. equal probabilities of segregation

2. independent assortment

3. random fertilization

4. high number of offspring

Know the formula for the number of possible gametes that a certain organism can produce. Using this

knowledge, how many genetically different gametes can humans produce?

2ⁿ , n=haploid number of a species

humans= 2²³= 8 million each parent

Define proband

proband is the individual who began a trait (first instance of a phenotype that led to a pedigree aka family tree)

In pedigrees, which shape is M vs F?

Male= square

Female= circle (hint “women are curvier”)

What symbol signifies affected individuals?

blue color

What symbol signifies a deceased individual?

slash through the square or circle

What symbol signifies they are a heterozygous carrier?

a dot in the center of the shape

True or false? Albinism is an example of an autosomal recessive trait, which appears equally in both

sexes

True!

How can you tell, based on a pedigree, if a phenotype is sex linked or autosomal?

Autosomal if the number of M & F affected are roughly equal

Sex linked:

• X-linked= males mostly affected, but some women are affected

• Y-linked= ONLY males are affected & if a father has it, ALL of his sons have it

How to know if a phenotype is dominant or recessive?

If dominant, it is present in every generation

Do question 4 and 10 on the review for this Lesson

answers on ipad

Is a widow’s peak an autosomal dominant or recessive trait?

dominant

What are wild type alleles? Are they usually recessive or dominant?

the standard, most common version of a gene found in a natural population

• usually dominant

What is locus? How does this concept apply to Mendelian genetics?

location of a gene on a chromosome

• alleles occupy the same locus

• a trait is controlled by a single locus

What are the Modifications of Mendelian Ratios? (factors that modify the ideal ratios)

1. Genes can have many different alleles that interact differently

2. Gene Interactions

3. One gene can have many phenotypes

4. Genes and gender

5. Genes and environment

6. Genetic imprinting

7. Extranuclear inheritance

How many alleles of the same gene can an individual have vs a population?

Individiual can have max 2 alleles per gene

Populations can have MANY alleles per gene

What is incomplete dominance? What are the genotypic and phenotypic ratios?

Incomplete/partial dominance= one allele is not completely dominant over the other, this results in an offspring with a mix of mother and fathers phenotypes

genotypic & phenotypic= 1:2:1

Give an example of incomplete dominance in humans.

Tay-Sachs disease (TSD)- affected individuals lose HEXA enzyme - ability to metabolize lipids (fatal when aa)

Aa= 50% normal enzyme present = sufficient to survive

What is codominance? What are the genotypic and phenotypic ratios?

Both alleles are dominant, so both phenotypes are fully expressed in heterzygotes (not a mix)

geno&phenotypic= 1:2:1

Example of codominance in humans?

MN blood group

• when heterozygous, both M and N glycoproteins are present on RBC

In humans, the ABO blood groups are determined by three different alleles: i, I^B and I^A. The

combination of these alleles originates the A, B, AB and O blood types. Knowing that an organism can

only carry two alleles of a particular gene, how can you explain that three different alleles can combine

to produce four different blood types?

1. theres 3 alleles total: I^A, I^B, and I⁰

2. I^A and I^B are codominant

3. I⁰ is recessive to I^A and I^B

This creates 4 possible phenotypes/antigens:

1. A (I^AI^A or I^AI⁰)

2. B (I^BI^B or I^BI⁰)

3. AB (I^AI^B)

4. O (I⁰I⁰)

For the ABO blood system, what is the mode of inheritance (dominancy) of the phenotypes/antigens?

A & B dominant over O

A & B codominant

In snapdragon plants, pink flowers are caused by incomplete dominance. What will the phenotype of the

offspring be if you cross two pink flower plants?

1:2:1 red:pink:white

• because the pink flowers are heterozygous

What are lethal alleles? What does time of death depend on? What are the types of lethal alleles?

lethal to the individual when it is phenotypically expressed —> time of death depends on when the gene product is needed… won’t die until expressed

2 types:

1. Recessive lethal alleles (non-functional gene products)

2. Dominant lethal alleles (lethal when allele is present)

In mice, the yellow coat color is dominant, agouti coat color is recessive, and lethality is recessive (only lethal when homozygous for yellow).

In a cross between two yellow mice, what will be the color phenotype of the offspring?

2:1

yellow:agouti

NOT 1:2:1… bc homozygous Yellow is lethal

Dominant lethal alleles are, in most cases, eliminated from populations. In which case can they persist in

a population? Give an example from humans.

Eliminated easily because they commonly are lethal before sexual maturity, HOWEVER can persist if the gene product is not needed/expressed until after sexual maturity & reproduction

ie. Huntington’s Disease (late onset)

What are features of Huntington’s Disease? Cause?

• late onset (45+), so have already reproduced and passed on genes

• autosomal dominant

• lethal with just one HD allele (50% change inheritance)

Cause

• trinucleotide CAG repeat expansion

If both the mare and the stallion have overo coat color (heterozygous patches), what will be the chance that their foals will have the Lethal White Overo syndrome?

Dad= NO, Mom= NO —> 25% chance OO

What is epistasis?

expression of one gene or gene pair masks or modifies the expression of other gene(s)

means stoppage in greek

Give 3 types of epistasis

1. Homozygous recessive gene at one locus overrides alleles at other loci

2. Single dominant allele at one locus influences the expression of alleles at a second locus

3. 2 gene pairs complement each other so that at least one dominant allele at each locus is required to have particular phenotype

What are the allele combinations for lab color? What type of epistasis does this represent

Recessive Epistasis:

E gene is pigment deposition (will the color be deposited or not) gene & B is pigment color gene

• ie. BBEe

Black lab= BB, Bb, EE, Ee

Chocolate lab= bb, EE, Ee

Yellow lab= ee

For Recessive epistasis genes like the lab coat color, what is the phenotypic ratio when you cross two diheterozygotes?

9:3:4

black:brown:yellow

Imagine that you are a Labrador breeder, and you have a pair of dogs with known genotype for coat

color: your male has the genotype (bbEe) and your female (BBee). What are the colors of your two

dogs?

a. Your friend wants to buy a chocolate Labrador and you offer him to sell one of the puppies from

a cross between your dogs. Will your dogs be able to produce a chocolate puppy?

male= chocolate, female=yellow

a. no, 50% will be black and 50% will be yellow

Female \ Male	bE	be
Be	BbEe(Black)	Bbee (Yellow)

How many genes are involved in determining coat color in Labrador retrievers?

2

Bb= pigment color

Ee= will color be deposited or not

For epistasis when a dominant allele at one locus influences the expression of alleles at a second locus, what is the phenotypic ratio? example?

Pumpkin color!

Locus A dominates expression of locus B

• when locus A is recessive (aa), locus B can be expressed

• AA, Aa= white color

• aa —> BB (yellow) or Bb (green)

AaBb x AaBb

—> 12:3:1

—> A:B:b

—> first locus dom : second locus dom : second locus rec

Give example of how phenotypic expression can depend on the physical location of a gene AKA position effect

The Philadelphia Chromosome

• BCR & ABL genes share common regulatory region (after translocation of ABL gene)

• causes leukemia (continuous proliferation of cells)

What is pleiotropy? Give an example

one gene can affect multiple traits: the gene product is involved in multiple biochemical pathways/processes

ie.

• phenylketonuria deficiency: deficiency in phenylalanine hydroxylase which is needed to convert phenylalanine into tyrosine

  • mutations cause 3 traits: eczema, pigmentation detects, mental retardation

What are the terms we discussed so far for autosomal multiple allele/gene interactions that cause deviations to Mendelian crossings:

1. incomplete dominance

2. codominance

3. genes with miltiple alleles

4. lethal alleles

5. epistasis

6. pleiotropy

True or false? The gene responsible for the ABO blood group, when homozygous, can cause the

Bombay phenotype

False

Recessive Epistasis example:

Bombay phenotype is a recessive mutation in FUT1 gene/H gene

• the H gene produces the H antigen… H antigen is needed to have A or B antigen/blood type

• bombay phenotype has no H antigen —> mimics blood type O, but is not type O

What was the first direct proof of the chromosomal theory of inheritance?

discovery of X-linked inheritance mode

The locus for white eye color gene in Drosophila is present on the X chromosome, so males that carry

the white allele will always have white eyes. Females, on the other hand, can have red eyes (the

dominant phenotype) if not homozygous for the white allele (the recessive). Draw a cross between a white-eyed female

and a red-eyed male, including the F1 and F2 generations, with their respective phenotypic and genotypic

ratios

draw on ipad… check with AI

What is criss-cross inheritance?

males get their X-chromosomes from their mother and transmit it to their daughters

Are x-linked genes in males dominant, recessive?

neither!

hemizygous bc only has 1 X chromosome

Because males are hemizygous for X-linked genes, what does this mean for recessive allele expression?

recessive X-linked alleles are always expressed in males

Who do X-linked lethal alleles affect?

lethal to males

females are carriers (X2 can mask)

In a pedigree, if there are mostly males, but some women are affected by the phenotype of interest, is it X or Y linked?

X linked, passed from affected father to carrier daughter or from carrier mother to affected son

How are Y-linked traits inherited?

From father to ALL sons

ONLY males

In a pedigree, if there are ONLY/ALL males affected by the phenotype of interest, is it X linked or Y linked?

Y linked bc its only passed from affected father to ALL sons

What type of gene is color blindness in humans?

X linked! males are hemizygotes, so they will be colorblind when allele is present BUT women MUST be homozygous

affected mothers pass it on to their sons

sons pass on to carrier daughters

If a color-blind woman has children with a normal man, what will the phenotypes of the male and

female children be?

X-linked, so

all male kids are colorblind

all female kids are carriers

What is sex limited inheritance?

expression of specific phenotypes is limited to ONE sex ONLY

& expression is influenced by sex HORMONES

How do you explain the fact that only females produce milk in mammals? What kind of trait is milk

production?

this is sex limited inheritance

• milk produced only when have babies when gene interacts with sex hormones

Examples of sex limited inheritance

plumage in male and female birds

milk production in female mammals

mane in male lions

antlers in male deer

What kind of trait is tortoiseshell coat color in cats: sex limited, sex linked, or sex influenced?

sex linked

What is sex influenced inheritance? Which genotype shows sex influenced expression?

Gene expression level in heterozygotes is influenced by sex hormones

heterozygous genotype

Example of sex influenced inheritance?

Male pattern baldness

• both male and female can be Bb heterozygous for baldness, but only males are bald bc of hormones

What is penetrance? ie?

the % of individuals that have the genotype for a mutant phenotype AND express its phenotype

ie… if 5% of humans with the dominant allele for HD dont develop the disease, then penetrance is 95%

What is expressivity?

reflects the range of expression of a mutant phenotype

What causes expressivity ranges & penetrance of a gene?

1. influences of other genes

2. Environmental influence

3. both other gene AND environment

Your friend has a Siamese cat named Socks, and knows you are taking a Genetics class. She asks you

why her Siamese cat has black legs and ears but the rest of his body is light-colored. How can you

explain this phenomenon to your friend?

siamese cat fur color is temperature sensitive

• warmer parts of the body such as the abdomen are lighter colors

• cooler parts of the body such as the extremities are darker colors

Examples of temperature sensitive mutations

evening primrose — red at 23 C and white at 18 C

himalayan rabbit & siamese cat — pigmentation

Bacteriophages — ability to infect bacteria

Examples of disorders that are expressed based on time of onset — gene activity regulated in time

1. tay-sachs diseas (die at 3 yo)

2. duchenne muscular dystrophy (x linked, onset 3-5 years)

3. huntington disease (onset at all ages/late onset)

What is genetic anticipation?

onset and severity of genetic disorders tend to get worse with each successive generation

What type of DNA sequence is associated with genetic anticipation? Disorders?

applies to disorders caused by trinucleotide repeat expansion

• huntingtons Dz

• Fragile X Syndrome

• Myotonic Dystrophy

What is gene regulation?

changes in DNA sequences and the genetic code

What is epigenetic regulation?

controlling gene expression without changing DNA sequence

What is gene imprinting?

form of epigenetic regulation where gene expression depends on the parental origin

• the imprinted parent is the one whose allele is silenced

What are maternally imprinted genes?

maternal allele is epigenetically silences

paternal allele is expressed

What are paternally imprinted genes?

paternal allele is epigenetically silenced

maternal allele is expressed

How is genomic imprinting involved in Prader-Willi syndrome?

cause: maternal imprinting & deletion of paternal allele in chromosome 15

How is genomic imprinting involved in Angelman syndrome?

cause: paternal imprinting and deletion of maternal allele in chromosome 15

How are mitochondria inherited?

INHERITED MATERNALLY… all children inherit their mitochondria from their mothers

Why do mutations in the mitochondrial genome usually affect tissues with a high energy demand? Which tissues are these?

These tissues require lots of energy and mitchondria produce ATP

• brain and muscles

Where is the mitochondrial genome of clones inherited from? Where is the clones nuclear genome from?

mitochondrial= the egg cell

nuclear= the somatic body cell with desired genes

Smart Little Lena, a cutting horse, was cloned in 2006. Suppose you own all five clones and want to

register them in a breeder’s association, but the officials refuse to do so, stating that, since the horses all

have the same nuclear genome, they can’t be distinguished from each other. Using the knowledge

obtained in class, what experiments would you perform to genetically differentiate the clones?

genetically differentiate the cloned horses by analyzing their mitochondrial DNA (mtDNA) and epigenetic factors

• mitochondrial DNA comes from the egg donor, not from the animal with the desired cloned genes

• epigenetic modifications change over time based on distinct environmental factors, stress, and individual life experiences

True or false? Imprinted genes are randomly distributed in the genomes of plants and animals.

False

• in plants and animals, imprinted genes cluster together under the control of an imprinting control region (ICR)

True or false? When a gene is paternally imprinted, the maternal allele is expressed

True

What is the “maternal effect”?

offspring’s phenotype for a particular trait is controlled by mom’s gene products (mRNA/protein put into egg cytoplasm) present in the egg before fertilization

• aka, the kids phenotype is determined by the moms genotype or environment, not the kids own genes

What are the consequences of the “maternal effect” for the offspring?

the mothers mRNA is responsible for regulating early embryonic development & phenotype (and can influence lasting traits)

During the production of a transgenic plant, a new gene is introduced. This gene is integrated at random

into the genome. Some of the resultant plants show expression of the new gene and others do not,

despite the fact that it was confirmed that the gene had integrated into the genome of the plant. Can you

think of an explanation for this observation?

the position effect- expression of genes depends on the physical location of the gene on the chromosome

• chromosomal rearrangements —> can modify gene expression and trigger epigenetic silencing

Analyze the pedigrees in the review for this chapter (answers in slideshow), keep in mind, how can you determine the mode of inheritance for: autosomal Vs sex linked Vs mitochondrial; dominant, recessive, or hemizygous

Autosomal= evenly affects males and females

Sex linked=

• X-linked= males mostly affected, but some women are affected

• Y-linked= ONLY males are affected & if a father has it, ALL of his sons have it

Mitochondrial= an affected mother passes the trait to ALL of her children but an affected father passes it to NONE of his

Dominant= appears in all generations

Recessive= it skips generations and unaffected parents (carriers) have an affected child

Hemizygous=

• for X linked mutations, every shaded male is hemizygous for the mutated allele and unshaded are hemizygous for normal allele

• for Y linked mutations, all males are hemizygous for the mutated allele

What is OMIM?

online mendelian inheritance in man

• an online catalogue of human genes and genetic disorders

What is OMIA?

Online Mendelian Inheritance in Animals

• genes, inherited disorders, and traits in 562+ animals