Unit 6a: Mendelian Genetics &

Chromosomal Disorders

Gregor Mendel (mid 1800's) Mendel's work was done before the molecular basis

of chromosomal inheritance (i.e. meiosis and mitosis) was known.

His work formed the foundation from which subsequent work showed that genes existed on chromosomes and were indeed the inherited material passed on from generation to generation.

Mendel worked with pea plants for several reasons: 7 unique traits, most of which were “either/or” traits

(purple or white, wrinkled or smooth, etc) Closed flowers (prevented accidental pollination)

Characters Mendel Studied:

Character – a heritable feature (e.g. flower height) Trait – the variant for a particular character (e.g.

tall or short) So….

True-breeding – All offspring of a given plant are the same as the parent plant Either homozygous dominant (YY) or homozygous recessive (yy)

Hybridization – crossing (mating) of true-breeding varieties P generation – parental generation F1 generation – first generation F2 generation – second generation

Mendel's hypothesis included the following:

1. Alternate versions of genes (i.e. different alleles) account for differences in inherited characters

Gene for flower color is either purple or white

2. For each character, an organism inherits two alleles (one from each parent)

3. If the two alleles at a locus differ, one is dominant and one is recessive:

Dominant allele – determines organism's appearance

Recessive allele – no noticeable effect on organism's appearance

Law of Segregation Two alleles for a heritable character separate

(segregate) during gamete formation Thus egg or sperm (gametes) get only one copy

Law of Independent Assortment

Each pair of alleles of a given trait sorts itself independently of all other alleles of other traits Occurs during metaphase I (homologous pairs of each

chromosome line up) and metaphase II (sister chromatids of each chromosome separate) of meiosis

Homozygous – when the two alleles of a given trait are identical (e.g. PP or pp)

Heterozygous – when the two alleles of a given trait/gene are not identical (e.g. Pp)

Phenotype – physical trait; what you see (e.g. purple flowers)

Genotype – genetic makeup (e.g. PP or Pp) Example:

Pheno: purple, purple, white Geno: PP, Pp, pp

Punnett Squares

Monohybrid cross (one gene being looked at) PP (purple) x pp (white) (cross to F1 then cross F1 to F2) Phenotypic ratio; genotypic ratio

Dihybrid cross (two genes being looked at) YYRR (yellow round) x yyrr (green wrinkled) (cross to F1 then cross F1 to F2)

Types of Inheritence

1. Complete Dominance In the presence of at least one dominant allele,

the dominant phenotype will be expressed Ex: Pea plant flower color

PP – purple Pp – purple pp - white

2. Codominance An equal expression of both

(different) alleles results in a mixed phenotype

Examples: Blood type AB (both A antigens

and B antigens are expressed on blood cells)

Roan horses (both hair colors are present in equal numbers)

Non-Mendelian Types of Inheritance

3. Incomplete Dominance Phenotype is a blended version

of the two alleles Examples:

Snapdragon flowers: red (RR) x white (rr) yield all pink (Rr) flowers in F1 generation

Tay-Sachs disease: 2 copies of allele = death at early

age 1 copy of allele = brain cells produce

only ½ the enzyme in it's proper form (other ½ is mutated form)

4. Multiple Alleles A particular gene can have multiple (more than

two) but each individual only inherits two (one from mom and one from dad)

Example: Blood type (A, B, AB, O)

5. Sex-linked traits A gene located on either sex

chromosome is called a sex-linked gene (X in humans) Sex-linked gene (on X chromosome) Linked genes (genes that tend to be

inherited together on the same chromosome due to their close proximity)

Examples: Color blindness Hemophilia

6. Sex-limited traits Autosomal gene is present in both sexes but

expression depends on sex of individual (it’s dominant in one sex but recessive in the other)

Example: Baldness in males:

Man with one copy of gene will be bald Female needs two copies of gene to be bald

Milk production in females Man with one copy does not lactate Female with one copy lactates

5. Polygenic inheritance Many traits are the product of multiple genes and

their environment Examples:

Skin color, hair color Many genetic disorders (e.g. autism, cancer)

Extranuclear inheritance Some genes are passed from parent to offspring

without being part of nuclear chromatin Mitochondria (and chloroplasts in plants) are randomly

assorted into gametes and daughter cells In animals, mitochondrial traits are maternally inherited

Example: Leaf color in four o'clock plants Human mitochondrial disorders

Sex Chromosomes In humans, X and Y are the two

sex chromosomes In females (XX), one X is

inactivated in each cell (randomly) In males (XY), the X from mom is

always active X chromosome contains majority

of genetic information on sex chromosomes; Y chromosome is much smaller with only 70’ish genes

Gene linkage Genes adjacent (or close) on the

same chromosome tend to move as a unit; these genes are often termed “linked genes” Probability that they will segregate

as a unit is a function of distance between them

Mendel's laws of segregation and independent assortment only apply to genes on different chromosomes! Linked genes do not apply.

Gene Mapping based on recombination frequencies

Given the following table, construct a simple recombination map for the location of genes on a particular chromosome:

P and L – 30%

L and X – 5%

X and P – 35%

M and P – 10%

X and M – 45%

Chi-squared Test

Statistical test used to compare observed data with expected data to see if the null hypothesis (expected data) is within an acceptable range.

Practice Problems

*See separate sheet*

Mendel's work (circa 1850) showed existence of “hereditary factors”

Subsequent work showed these “factors” (i.e. genes) are located on chromosomes which are passed along from cell to cell via: Mitosis – occurs in somatic cells; results in 2 identical

diploid daughter cells Meiosis – occurs in germ cells; results in 4 non-

identical haploid daughter cells

Mutations• Mutations can arise from direct damage to DNA

OR from mistakes during meiosis

• Mutations can be:

Harmful Beneficial Neutral

A. Mutations directly to DNA

1. Mutation(s) during replication of DNA (S phase of cell cycle)

2. Environmental mutations carcinogens and/or toxins in environment modify bases on DNA strand

*In all cases, mutation will be passed on to all subsequent cells (unless mutation is

lethal)*

B. Mutations involving changes in chromosomes

1. Abnormal chromosomal number

Results from nondisjunction (members of a pair of homologous chromosomes do not move apart properly during meiosis II)

Aneuploidy – abnormal number of chromosomes Monosomic – only one copy Trisomic – three copies

Examples Trisomy 21 (aka Down's

Syndrome) Klinefelter Syndrome (XXY)

Male sex organs are present but small; male is sterile

Breast enlargement and other female body characteristics are often present

Turner's Syndrome (aka Monosomy X) Females are sterile; if given

estrogen replacement therapy, secondary sex characteristics will develop

2. Alterations in chromosome structure Deletion – chromosomal fragment is lost Duplication – chromosomal fragment is

duplicated (in tandem or in reverse) Inversion – part of chromosome breaks, inverts

180, and reinserts itself into same place on chromosome

Translocation – part of chromosome breaks apart and re-inserts into another part of chromosome or another chromosome entirely

Examples

“cri du chat” - deletion in chromosome 5 Child is mentally retarted, small head with unusually

facial features, cry like a distressed cat Chronic myelogenous leukemia (CML) –

translocation between chrosomes 22 and 9 Cancer of bone marrow affecting young children to

young adults