Human Genetics (Outline) • Define “karyotype”: autosomal chromosomes and sex chromosomes • Mendel and terminology. • Medelian Pattern of single autosomal gene inheritance; Punnett square • Test cross and purpose. • Pedigrees used to determine the pattern of inheritance and make genetic

predictions. • Gender determination in mammals; X- or Y-linked genes. Pattern of

inheritance of sex-linked genes • Explain X-inactivation in females. • Inheritance of mitochondrial genes • Phenotypic expression and multi-factorial traits Mendelian characters and

provide examples for each: incomplete dominance, co-dominance & multiple allele, pleiotropy, polygenic inheritance, environmental effect.

These are sex chromosomes The chromosome pairs 1 trough 22 are autosome

Karyotype; display of condensed human chromosomes

Patterns of Inheritance Gregor Mendel

- Studied variation in plants, patterns of

inheritance in garden peas - Used math to explain biological phenomena

Terminology Character or characteristic: a heritable

feature e.g. flower color Trait: variant of the character e.g. purple or

white Mendel focused on characters with two

variants “either-or” traits

Mendel had control over which plants he crossed Colored Cotton Campbell video

http://www.dnaftb.org/

dnaftb/1/concept/

Mendel started with True-breeding plants F1 generation F2 generation F2 ratio

Purple flower- dominant trait

White flower- recessive trait

Mendel worked with pea plant characteristics with two traits each

Mendel was looking for a model that can account for the 3:1 ratio that he observed in the F2 generation

Mendel’s Model

1. An organism inherits two alleles (one from each parent).

2. One allele is dominant and the other is recessive

3. Mendel’s first law of segregation: the two alleles segregate (separate) during gamete formation

4. Mendel’s second law of independent assortment

Mendel's First Law – Segregation

A Punnett square predicts the results of a genetic cross between individuals of known genotype.

Vocabulary used in Genetics An organism with two identical alleles is

homozygous for that character. Organisms with two different alleles for a character

is heterozygous for that character. A description of an organism’s traits is its

phenotype. A description of its genetic makeup is its

genotype.

Test Cross

Used to determine the genotype of a dominant trait

Figure 4.9

Mendel's Second Law – Independent Assortment

Mendelian characters of humans

Eye Color Wild-type human eye color is brown - Blue and green eyes stemmed from

mutations that persisted

The surface of the back of the iris contributes to the intensity of eye color

Figure 4.8

Pedigree Analysis

• A pedigree can help us understand the past and to predict the future.

• We can use the normal Mendelian rules,

to predict the probability of specific genotypes and phenotypes.

Examples of Genetic Disorders http://www.ygyh.org/ Tay-Sachs Sickle Cell Disease Cystic Fibrosis Huntington Disease

Gender • Maleness or femaleness is determined at

conception

• Another level of sexual identity comes from the control that hormones exert on development

• Finally, both psychological and sociological components influence sexual feelings

Sex determination in Mammals: the X-Y system

Karyotype designation: 46, XY (male)

46, XX (female)

Germ cells in testes (XY) produce sperms with X: 50% Y: 50% Germ cells in ovaries (XX) produce only X eggs

• The X chromosome have genes for many

characters unrelated to sex • Each conception has about a fifty-fifty chance of

producing a particular sex

The inheritance of genes of X chromosome follows special rules, because:

• males have only a single X chromosome • almost all the genes on the X have no

counterpart on the Y • any gene on the X, even if recessive in

females, will be expressed in males. • Genes are described as sex-linked or X-

linked.

X-linked Recessive Traits Possible genotypes XAXA − Homozyogus wild-type female XAXa − Heterozygous female carrier XaXa − Homozygous mutant female XAY − Hemizygous wild-type male XaY− Hemizygous mutant male

Examples of X-linked Recessive Diseases

Hemophilia A, a blood clotting disorder caused by a mutant gene encoding the clotting factor VIII

Duchenne muscular dystrophy http://www.ygyh.org Color blindness (X-linkage) http://www.biology.arizona.edu/human_bio/proble

m_sets/color_blindness/color_blindness.html

Human Chromosomes Homologous autosomes: 22 pairs = 44 chromosomes Sex chromosomes one pair XX or XY (X and Y share partial homology) Dose of expressed genes?

X-inactivation

In females, only one of the X chromosomes is active. The second is inactivated The inactive X chromosome appears as a condensed

chromosome during interphase (Barr body) http://users.rcn.com/jkimball.ma.ultranet/BiologyPage

s/S/SexChromosomes.html

Figure 6.12

X Y

X XX XY

Xh XhX XhY

Hemophilia A

In XhX heterozygote female, which X is active?

X-inactivation is random: 50% of cells Xh 50% of cells X

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/SexChromosomes.html

X Inactivation A female that expresses the phenotype

corresponding to an X-linked gene is a manifesting heterozygote (calico cats)

Figure 6.12

Y-linked genes

The Y chromosome in males has 70 to 200 gene genes whose protein products are involved in:

a. control of changing sex of the fetus from female to male

b. development of male testes c. male fertility http://ghr.nlm.nih.gov/chromosome=Y

Factors Affecting Phenotypic Expression of Mendelian inherited characteristics

1. Incomplete dominance 2. Multiple alleles- co-dominance 3. Pleiotropy 4. Polygenic inheritance 5. Environmental effect 6. Epigenetic factors

Genotypic ratio same as phenotypic ratio

1. Incomplete dominance

Genotypes: HH

Homozygous for ability to make

LDL receptors

Hh Heterozygous

hh Homozygous

for inability to make LDL receptors

Phenotypes:

LDL LDL receptor

Cell

Normal Mild disease Severe disease

Incomplete dominance affects severity of disease

2. Multiple alleles, the human ABO blood system

Multiple alleles of the ABO blood system - Three alleles, IA, IB, and I.

Both the IA and IB alleles are dominant to the i allele

The IA and IB alleles are co-dominant to each other.

- Because each individual carries two alleles,

there are six possible genotypes and four possible blood types.

3. Pleiotropy - A single gene may affect many phenotypic characteristics involving multiple systems - Sickle cell Disease http://www.ygyh.org/

Individual homozygous for sickle-cell allele

Abnormal hemoglobin crystallizes, causing red blood cells to become sickle-shaped

Sickle-cell (abnormal) hemoglobin

Sickle cells

Breakdown of red blood cells

Clumping of cells and clogging of

small blood vessels

Accumulation of sickled cells in spleen

Physical weakness

Anemia Heart failure

Pain and fever

Brain damage

Damage to other organs

Spleen damage

Impaired mental

function

Paralysis Pneumonia and other infections

Rheumatism Kidney failure

Quantitative characters show additive effect of multiple genes, e.g skin color and height in humans

4. Polygenic inheritance

5. Environmental effects

Phenotype of Hydrangea flower color

• Blue flowers in highly acid soil • Pink flowers in neutral or slightly acid soil

6. Epigenetic factors Gene expression is impacted by chemical

modification of chromatin • DNA methylation • histone deacetylation

Inheritance of nuclear and mitochondrial or chloroplast DNA

• Nuclear DNA- diploid on linear segmented chromosomes

• Mitochondria and Chloroplasts- single haploid circular chromosome

Replicate independently of nucleus

• Defects in mitochondrial genes are passed through the maternal lineage

During fertilization sperm brings only the nuclear DNA, all mitochondrial DNA is maternal from the egg.

No Mendelian patterns of inheritance Can be used to determine maternal lineage