Genetics Exam 2 Review

Chapter 4

Chapter 4

Sex-determination and Sex-linked characteristics

Environmental Sex Determination

Sex genes are not the only factors that influence sex determination, environment can also be a factor

Bearded Dragons

• Males are ZZ and females are ZW

• ZZ bearded eggs incubate at temperatures lower than 32C as males and higher temperatures as females

• ZZ embryos at higher temperatures will develop as females

• Mating of male ZZ and female ZZ will produce ZZ offspring

• ZW embryos will always be female

Heterogametic

two kinds of gametes of which one produces male offspring and the other female offspring (XY)

Homogametic

forming gametes which all have the same type of chromosome (XX)

Genetic sex determination

where the genotype at one or more loci determine the sex of the individual

The fundamental difference between male and female gametes

is size: males are small, and females have large gametes

Polygenic

more than one chromosome determine if male or female

Sex Determining System: XX-XO

• Females: XX, Males:XO

• Heterogametic Sex: male

• Organisms: some grasshoppers and other insects

Sex Determining System: XX-XY

• Females: XX, Males: XY

• Heterogametic sex: male

• Organisms: insects, fish, amphibians, mammals, reptiles, humans

Sex Determining System: ZZ-ZW

• Females: ZW, Males: ZZ

• Heterogametic sex: females

• Organisms: Butterflies, birds, some reptiles/amphibians

The term sex refers to sexual phenotype → Male/Female

• Cells of human females have 2 X chromosomes and cells of males have 1X and 1Y chromosome

• Rate individuals have male anatomy although their cells contain two X chromosomes. Even though these individuals are genetically female, we refer to them as male because their sexual phenotype is male

Hermaphrodism

an organism that have both male and female reproductive systems

• Monecious “one house”

• Dioecious “two houses” individual organism that has either male or female reproductive structures

Genetic Sex Determination

Where the genotype at one or more loci determine the sex of an individual.

• In mammals the SRY gene (Sex-determining region Y) on the Y chromosome

Primary Pseudo-autosomal region

• The X and Y chromosomes are homologous only at the pseudo-autosomal regions, which are essential for X-Y chromosome pairing in meiosis in the male

Sex Determining in Drosophila

• An X chromosome-autosome balance is used

• Drosophila have 3 pairs of autosome, and one pair of sex chromosomes

• Like humans, XX is female and XY is male. Unlike humans Y does not determine the sex

• An XXY fly is female and an XO fly is male. The sex of the fly results in the ratio of the number of X chromosomes to the number of sets of autosomes

Results of Sex Determination in Drosophila

• In normal (diploid) female drosophila, A=2 and X=2.

  • The X:A ratio is 1.0

• In a normal (diploid) male drosophila, A=2 and X=1

  • The X:A ratio is 0.5

• In the case of aneuploidy (abnormal chromosome numbers)

  • When X:A ratio is >/= 1.0 the fly is female

  • When X:A ratio is </= 0.5 the fly is male

  • When the X:A ratio is between 0.5 and 1.0 it results in a sterile intersex fly with male and female traits

Drosophila

• Although the sexual phenotype of a fruit fly is predicted by X:Y ratio, sex is actually determined by the genes on the X chromosome

  • Example: XYAA, 0.5 ratio, SxI gene off, Phenotype is male

  • Example: XXAA, 1.0 ratio, SxI gene on, Phenotype Female

Mosaicism

Seen on Turner Syndrome. Some cells that are XX and others that are XO

Turner Syndrome

Karyotype: XO

• Symptoms/Signs: No menstruation, brown spots, elbow deformity, poor breast development, rudimentary ovaries, gonadal streak, wide neck

Klinefelter Syndrome

Karyotype: XXY, XXXY, XXXXY, XXXXXY, etc

Symptoms/Signs: Small tests, female-type pubic hair, breast development (30% of cases), tall stature, low IQ, osteoporosis

Triple X Syndrome

Karyotype: XXX

• Also called 47XXX, 47XXX syndrome, Triplox syndrome, Trisomy X, XXX syndrome

• Symptoms/Signs: Tall, thin, delayed language development. intelligence within normal range, regular menstruation, and are fertile, >3X results in sever mental retardation

XYY Males Medical Concerns

• It is unclear if there are special medical concerns in individuals with XYY

• Some studies suggest there could be slightly higher rate of seizers and tremors

XYY Males Learning and Behaviors

• Most children with XYY have IQ scores that fall within the average range, or slightly below the average, but there is a wide range of learning abilities

• Some children have delays in language development or reading skills

• Behavior concerns may include attention problems and hyperactivity (ADHD), autism, and difficulty with social skills

Androgen Insensitivity Syndrome

• It is a genetic disorder that cause XY fetuses to become impassive to androgen and male hormones

• They are born appearing externally female even if they are genetically male

• Inside there is an undersized vagina, with no uterus, fallopian tubes, or ovaries

• There are testicles in the abdomen or the groin area

• Complete androgen insensitivity syndrome is frequently confirmed at puberty when an individual is supposed to start menstruating but does not

Androgen Insensitivity Syndrome Pt2

• This syndrome demonstrates that there are several genes that influence male and female characteristics

• secondary sex characteristics are presented on autosomes

• Androgen receptors deficient

• X-linked recessive- gene for receptor testosterone on X-chromosome

• Female carriers, males are affected

Role of Sex Chromosomes

1. The X chromosome contains genetic information essential for both sexes, at least one copy of an X chromosome is required for human development

2. The male-determining gene is located on the Y chromosome. A single copy of this chromosome, even in the presence of several X chromosomes, usually produces the male phenotype

3. The absence of the Y chromosome usually results in female phenotype

4. Genes affecting fertility are located on the X and Y chromosomes. A female usually needs at least two X chromosomes to be fertile

5. Additional copies of the X chromosome my upset normal development in both males and females, producing physical problems and intellectual disabilities that increases as the number of extra X chromosomes increases

Sex-Linked Characteristics

• Thomas Morgan carries his experiments using the fruit fly drosophila

• Investigated transmission genetics of white eyes in fruit flies

• Hemizygous- having one copy of a gene instead of two- all the copies on the single X-chromosome in the male are hemizygous

If white eye mutation is carries on X chromosome?

Females or males could have white eyes

What happens if white eye mutation is carried on the Y chromosome

All males would have white eyes and all females would have red

What would be the predicted phenotype ratios if this was not a sex linked trait but an autosomal trait?

The ratio would be 3:1 not 2:1:1

Morgan carries out another cross with the same mutation

1. White eye male (XwY) with homozygous red eye female (X+X+). Instead of all red eyed F1, offspring were 1234 red eyed and 3 white eye males

2. When his student Calvin bridges did the reciprocal cross with white eyed females and red eyed male → 5% of male offspring had red eyed while 5% of female offspring had white eyes

Calvin Bridges Theory

Non-disjunction of the X chromosomes could result in the 5% of male offspring having red eyes and the 5% of females having white eyes

Non-Disjunction

happens when homologous chromosomes fail to move apart toward the opposite poles of the cell in either anaphase 1 or 2

What would happen if a X+Xc female mated with a X+Y male? or XcY male?

1. Ratio is 2:1:1 phenotype ratio

2. Ratio is 1:1:1:1 phenotype ratio

The X and Y chromosome pair in meiosis

the small region they are homologous exhibit autosomal patter of inheritance rather than sex-linked

→ the non-hemizygous region

In humans…

the alleles for certain condition like hemophilia and muscular dystrophy are x-linked. These diseases are much more common in men than they are women due to their X-linked inheritance pattern

Z-linked characteristics: Example Indian blue peafowl

• Males are homozygous or heterozygous

• Females are heterogametic and have one Z sex-linked alleles and one W allele

• Zca+ allele is wild type blue plumage

• Zca allele is recessive cameo plumage

• Organisms with ZZ-ZW sex determination, the female inherits W from her mother and her Z chromosome and alleles from her father

• The male inherits one Z-linked chromosome from his mother and one from his father

Evolution of the Y chromosome

• Y-chromosome sequence have been used as markers to track genetic relationships and migration among different populations

• Female lineage→ mitochondrial DNA is used to track lineages

• An autosomal pair of chromosomes, one chromosome mutated resulting in maleness

• Mutations at other genes affected male characteristics

• Supression of crossing over keeps genes from male traits linked to a male-determining gene

• Over time, lack of crossing over between the X and Y chromosomes leads to the degeneration of Y

X inactivation and dosage compensation

• Females 2X and 2 copies of autosomes

• Males 1X and 2 copies of autosomes

• Males are producing smaller amounts of proteins encoded by X-linked vs autosomal genes- which could be detrimental

• In fruit flies→ males X chromosome increase activity of genes

• In mammals → X inactivation → Barr bodies so that expression of X-linked and autosomal genes are balanced for both males and females

Barr Body

Inactive X chromosome

Lyon Hypothesis by May Lyon in 1961

• Random X inactivation takes place in early development and is controlled by Xist gene

• After inactivation, it remains inactive in that cell and in all somatic cells from that line

• Mosaic expression in X-linked characteristics in heterozygous females (daughters will also have one X inactivated which X it is is random)

Barr bodies equation

Number of X’s- Number of Barr bodies= 1X left

Chapter 5

Extensions and Modifications of Basic Principles

Examples of Complete Dominance

• Dwarfism

• Eye Color

• Mendel’s peas

Incomplete Dominance

• Results in the genotype and phenotype ratios are the same

• Hence dominance is the way the genes are expressed but not how they are inherited

• Genotype is heterozygous and phenotype falls in between (If the phenotype of the heterozygous falls between the phenotypes of the two homozygous, dominance is incomplete)

Concepts

• Incomplete dominance is exhibited when the heterozygote has a phenotype intermediate between the phenotypes of the two homozygotes.

• When a trait exhibits incomplete dominance a cross between two heterozygotes produces a 1:2:1 phenotype ratio in progeny

Codominance

Heterozygous expresses the phenotype of both homozygous

• Blood type

• Sickle cell anemia

• Cystic fibrosis

Cystic fibrosis

Heterozygous individuals have one functional gene and this allows normal chloride ion transport

While homozygous for cystic fibrosis do not have enough protein, or no protein, or altered protein preventing ion transport

Blood Type

• RBCs do not react with the recipient antibody remain evenly dispersed. Donor blood and recipient blood are compatible

• Blood cells that react with the recipient antibody clump together. Donor blood and recipient blood are not compatible

• AB universal acceptor

• O universal donor

Codominance

1. Definition

2. Effect of the Hybrid

3. Effect of the allele

4. Expressed phenotype

1. The phenomenon where the offspring receives both the parents genes as a combination of both genes

2. Independent effect

3. Both alleles are equally conspicuous

4. Both parental characteristics expressed in unequal proportions

Incomplete Dominance

1. Definition

2. Effect of the Hybrid

3. Effect of the Allele

4. Expressed phenotype

1. The phenomenon where neither one of the parent genes is expressed but a combination is expressed

2. Intermediate of the two alleles

3. One allele is more conspicuous over the other

4. None of the parental characteristics is, the phenotype is a novel one

Expressivity vs Penetrance

• Penetrance is defined as the percentage of individual organisms having a particular genotype that expresses the expected phenotype

• Expressivity is defined as to the degree in which a trait is expressed

• Incomplete penetrance: heterozygous express phenotypes of both homozygotes

Penetrance

1. Definition

2. Measurements Taken

3. Variability

1. Percentage of individuals with a given genotype who exhibit the associated phenotype with that genotype

2. A population

3. Statistical variability among a population of genotypes

Expressivity

1. Definition

2. Measurements Taken

3. Variability

1. The intensity of the phenotype in an individual

2. A single individual

3. Individual variability

Pt2

• Some genes in an organism are known to cause death of the organism. The genes are either dominant or recessive, but MUST be homozygous

• Alleles of a lethal gene show deviation from normal Medelian inheritance

• Lethal alleles are produced when a mutation in a usual allele results in a phenotype, when expressed, is fatal to the organism

• Ex: Cystic fibrosis, Sickle Cell Anemia

Types of Lethal Alleles

1. Early onset: Lethal alleles which results in early death of an organism during embryogenesis

2. Late Onset: Lethal genes which have delayed effects so that the organism can live for some time but eventually succumb to disease

3. Conditional: Lethal alleles which kill organism under certain conditions. Ex: temperature sensitive

4. Semi-Lethal: Lethal alleles which kills only some individuals in the population but not all

Multiple Alleles

• The alternative forms of the same gene, so they influence the same trait

• The wild type allele is mostly dominant over mutant alleles

• The wild type is considered the standard and all other alleles are considered variants

• Multiple alleles follow mendelian genetics of chromosome segregation and independent assortment

Compound Heterozygous

two different mutations at a particular gene (can be cis or trans)

Ex: CFTR locus

Epistasis: Gene Interaction

• Epistatic interactions happen when an allele of one gene modifies or prevents the expression of alleles at another gene

• Epistatic interactions often arise because two or more different proteins participate in common cellular function

• Ex: enzymatic pathway

Pt2

• Phenotype expression is a collective effort of two or more loci

• At least two traits involved

• Not dominating but masking! They do not influence each other

No Interaction (9:3:3:1 Ratio)

• Cross involving color of Drosophila

• Results show that the genes are not undergoing epistatic interaction with one another

Dominant Epistasis

Occurs when the presence of a dominant allele at one gene locus masks the effects of alleles at another locus

• Ex WwYy (white) wwYy (yellow)

• The dominant W allele masks the color of the organism

Recessive Epistasis

Occurs when the recessive allele of one gene locus masks or prevents the phenotype expression of allele at another gene locus

• Ex: BbEE (brown) BBEE (black) BBee (yellow)

• The ee phenotype masks the color brown or black from being expressed

Bombay Phenotype and Epistasis

• The Bombay phenotype for ABO blood groups is an example of epistasis

• Homozygous recessive condition at one locus masks the expression of second locus

• Individual with the Bombay phenotype have the genes to make the A or B antigen at one loci but lack the genes to produce H substance at another loci

• No H antigen give you the O phenotype!

• Genes at both the H locus and AB locus determine the ABO blood type

Duplicate Recessive Epistasis

1. A dominant allele is required to create Enzyme 1 which converts A→B

2. A dominant allele is required to create Enzyme 2 which converts B→C (pigment)

3. Absence of a dominant allele for A or B compounds results in albinism so phenotype required for pigment is A_B_

Ratios

1. 9:3:3:1

2. 9:3:4

3. 12:3:1

4. 9:7

5. 9:6:1

6. 15:1

7. 13:3

1. None

2. Recessive Epistasis

3. Dominant Epistasis

4. Duplicate recessive epistasis

5. Duplicate Interaction

6. Duplicate dominant epistasis

7. Dominant and Recessive epistasis

When ratios do not meet your typical dihybrid cross try this formula to determine ratios

(# of progeny with a phenotype)/(Total # of progeny) x16

Complementation Test

• Is used to determine whether two mutations occur at the same loci or at different loci. Mutant alleles of the same gene fail to compliment one another, while alleles of different gene do complement one another

Sex Influenced

Se influences autosomal genes inherited by Mendelian principles

• Expressed differently in sexes. Examples beards of goats in males show in heterozygous but not in female heterozygous

Sex Limited

• Sex limited autosomal genes inherited by Mendelian principles

• Expressed only in one sex

• Ex: Hen feathering refers to the phenomenon of a male having a female plumage

Cytoplasmic Inheritance

Genes encoded in chloroplasts and mitochondria

• The human mitochondria contains 37 genes

• Differs from nuclear inheritance- where zygotes inherit from both parents

• Mitochondrial inheritance comes from the egg?

• Reciprocal crosses for cytoplasmic traits yield different results

• LHON disease causes optic neuropathy: inherited through mother to all offspring

• Degree of expressivity depends on the number of mutated mitochondria (different amounts in each egg)

Example: Stem/Leaf color inherited by plant

Conclusion: The phenotype of progeny is determined by the phenotype of the branch from which the seed originated, not from the branch where the pollen originated

• 4-o’clock plant offspring phenotype completely determined by cytoplasmic inheritance

• Variegated leaves- during chloroplast inheritance some cell inherited the mutated opDNA

Genetic Maternal Effect

• Arthur Boycott studying coiling in snail shells found coiling could be “dextral” clockwise, or “sinistral” counterclockwise

• Did not seem to follow Mendel’s principle

• Phenomenon was determined from maternal genotype “maternal gene effect”

• Proteins encoded by her nuclear genotype are left in the egg which influences offspring development

Genetic Imprinting

• Genomic imprinting is a process of silencing genes through DNA methylation→ known as epigenetics

• The repressed allele is methylated while the active allele is unmethylated

• The stamping process is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA

• The purpose of imprinting on maternal and paternal chromosomes is to ensure parent-of-origin specific expression after fertilization

• Both males and females pocess the gene→ the key to whether the gene is expressed is the sex of the parent transmitting the gene. Ex: Prader-Willi syndrome

Prader-Willi Syndrome

• On chromosome 15

• The paternal allele is active and its protein product stimulates fetal growth

• The maternal allele is silent. It produces no protein product to further stimulate fetal growth

• The size of the fetus is determined by the combined effects of both alleles

Phenotype Determined By

1. Sex-link characteristic

2. Sex-influences characteristic

3. Sex-limited characteristic

4. Genetic maternal effect

5. Cytoplasmic inheritance

6. Genomic Imprinting

1. Genes located on sex chromosomes

2. Autosomal genes that are more readily expressed in one sex

3. Autosomal genes whose expression is limited to one sex

4. Nuclear genotype of the maternal parent

5. Cytoplasmic gene which are usually inherited from only one parent

6. Genes whose expression is affect by the sex of the transmitting parent

Environmental effects on Phenotype

• Fruit fly vestigial wings develop longer wings when temperature is raised to 31C→ temperature dependent mutation

• Himalayan allele in rabbits- produce dark fur on the nose, ears, and feet at temp. of 25C or lower

• The enzyme is functional only in cells during lower temperatures. It is a temperature sensitive allele

Inheritance of Characteristics

• Discontinuous characteristics: characteristics which have a few easily distinguished phenotypes. Ex: blood types

• Continuous characteristics: wide range of characteristics. Ex: height

• Quantitative characteristics: many possible phenotypes and may involve a large group of loci- polygenic characteristics

• Pleiotropy: one gene affects multiple characteristics. Ex: coat color in dogs

• Multifactorial characteristics: genes affected by environmental factors. Ex: height dependent on nutrition

Chapter 7

Linkage, Recombination and Eukaryotic Gene Mapping

Harriet Creighton and Barbara McClintocle

• Obtained evidence of physical exchanges between chromosomes

• They investigated two traits on chromosome 9

• Found strain of corn had a densely staining knob and an extra chromosome end on chromosome 9, they were able to distinguish the homologous pair and prove crossing over when crossed with recessive strain

Linked genes

• Genes located close together on the same chromosome

• Linked genes segregate as a unit in meiosis 1

• Linked genes in meiosis 2 will assort independently (if crossing over occurs half will be recombinant)

• Represented as AB/ab

Using a testcross too figure out arrangement of linked genes

Coupling

• Cis configuration (PB/pb)

• Wild type alleles found on one chromosome

• Mutant type alleles found on the other

Repulsion

• Trans configuration (pB/Pb)

• Each chromosome contains one wild type and one mutant allele

Calculating Recombinant Frequency

(# of recombinant progeny/ total # of progeny) x100

Recombinant frequency provides us information about the alleles combinations

When predicting outcomes total =1. The recombinants will be the same value and nonrecombinants will be the same value

Genetic Maps

• Map units are measured in centiMorgans (cM)

• One map unit equals a 1% recombination frequency

• Map distances are additive

• Shows arrangements of genes

• Recombination frequencies cannot distinguish between genes on different chromosomes and genes located far apart on the same chromosome

• Does not reveal double crossovers take place → are more frequent between genes that are far apart

• Hence genetic maps based on short distances are more accurate

Constructing a Genetic Map with a 2-point Cross

Recombination frequency >50→ Independent assortment and are possibly on different chromosomes

Look over how to map in notes

Constructing Genetic Map with 3 point genetic map

1. Identify the nonrecombinant progeny (two most numerous)

2. Identify the double-crossover progeny (two least numerous)

3. Compare the phenotypes of double-crossover progeny with the phenotypes of nonrecombinant progeny. They should be alike in two characteristics and different in one

4. The characteristic that differs between the double crossover and the nonrecombinant progeny is encoded by the middle gene

   Look over how to perform in notes

Topoisomerase enzyme

“II” help with recombination by relieving torsional stress of DNA

• Two-strand double crossover= 0% detectable recombination

• Three-strand double crossover= 50% detectable recombination

• Four-strand double crossover= 100% detectable recombination

Effects of Multiple Crossovers

• Multiple crossovers can go undetected

• When genes are very close together, multiple crossovers are unlikely

• Genetic distances based on recombination rates of genes close together correspond to the approximate physical distances on the chromosome

• As the distance between genes increases, multiple cross over are likely but discrepancy between physical distances increases

• To correct for discrepancy, scientists created a Poisson distribution: relates probability of recombination with map distance

LOD Score

LOD=Z= log10(Probability of birth sequence given/probability of birth sequence with no linkage)

• By convention a LOD score >3.0 is considered evidence for linkage

• LOD score < -2 is considered evidence to exclude linkage

  Look at example calculation in notes

Genetic Markers

• Observable phenotypes whose inheritance could be studied

• In 1980 molecular markers called RFLPs (Restriction Fragment Length Polymorphisms) made it possible to examine DNA variations

• DNA was cut with restrictive enzymes

• Later methods were developed for detecting variable lengths of short DNA repeat sequences in tandem

• Can study these molecular markers in relation to phenotype and recombination between markers

• More than half of previously identified human VNTR loci are located near or within genes

Haplotype

• A group of genes within an organism that was inherited together from a single parent and evolutionary genetics:

• Some haplotypes will be lost or mutated, resulting in increased linkage disequilibrium

• Suppose that there were four common haplotypes in a genomic region in the past

• Assume that a functional mutation occurred on a particular haplotype

• After some generations the haplotypes of the current population are just a mixture of the common

• The haplotypes from affected individuals might share some segments from the common ancestral haplotypes in the area where the functional mutation occurred

• Haplotypes are markers used to trace evolutionary genetics

Linkage Disequilibrium (LD)

• Is a population based parameter that describes the degree to which an allele of on genetic variant is inherited or correlated with an allele of a nearly genetic variant within a population

• Crossing over breaks up the association between alleles in a haplotype reducing the linkage disequilibrium between them. When loci are far apart, linkage disequilibrium breaks down quickly

• When loci are close together crossing over is less common and linkage disequilibrium persists longer

Single Nucleotide Polymorphisms (SNPs)

• Are DNA sequence variations occurring when a single nucleotide in the genome differs in paired chromosomes

• Some SNPs in the coding region change the amino acid sequence of a protein, and others in coding region do not affect the protein sequence

• About 60% of crossovers take place in hotspots in the human genome

• Hotspots are located near the genes but not within active genes

Detecting Gene Location

Somatic Cell hybridization

• Separates a chromosome of interest from the full chromosome complement

• Chromosome number stabilizes after loss

• Human chromosomes in the mouse genomes make it possible to assign gene to specific chromosomes

• The hybrid cell can be screened and the human gene can be detected by looking either for the gene itself or the protein it produces

Deletion Mapping

Is a specialized genomic mapping technique that enables scientists to determine the location on a specific gene on a chromosome

Marker

Gives you close length of where the gene is located

Percentage of recombination for linked genes

1-2%

Fluorescence in situ hybridization (FISH)

Can detect specific sites of specific genes in metaphase or interphase cells using a probe that is fluorescent

Chapter 6

Pedigree, Analysis, Applications, and Genetic Testing