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.

• Non-genetics phenotypic expression: environmental effect and epigenetics

These are sex chromosomesThe chromosome pairs 1 trough 22 are autosome

Karyotype; display of condensed human chromosomes

Patterns of InheritanceGregor Mendel

- Studied variation in plants, patterns of inheritance in garden peas

- Used math to explain biological phenomena

TerminologyCharacter 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 generationF2 generationF2 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 Model1. An organism inherits two alleles (one

from each parent).2. One allele is dominant and the other is

recessive3. Mendel’s first law of segregation: the

two alleles segregate (separate) during gamete formation

4. Mendel’s second law of independent assortment

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

Vocabulary used in GeneticsAn 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

Mendelian characters of humans

Eye ColorWild-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 Disordershttp://www.ygyh.org/

Tay-SachsSickle Cell DiseaseCystic FibrosisHuntington 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 and orientation

Sex determination in Mammals:the X-Y system

Karyotype designation: 46, XY (male)46, XX (female)

Germ cells in testes (XY) produce sperms withX: 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 TraitsPossible genotypes

XAXA −Homozyogus wild-type femaleXAXa −Heterozygous female carrierXaXa −Homozygous mutant female

XAY − Hemizygous wild-type maleXaY− 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 dystrophyhttp://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 chromosomesSex 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/BiologyPages/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 InactivationA 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 testesc. male fertility

http://ghr.nlm.nih.gov/chromosome=Y

Factors Affecting Phenotypic Expression

Genetic characteristics inherited in a Mendelian fashion

1. Incomplete dominance 2. Multiple alleles- co-dominance3. Pleiotropy4. Polygenic inheritance

Non genetic factors affecting phenotype1. Environmental effect2. Epigenetic factors

Genotypic ratio same as phenotypic ratio

1. Incomplete dominance

Genotypes:HH

Homozygousfor ability to make

LDL receptors

HhHeterozygous

hhHomozygous

for inability to makeLDL receptors

Phenotypes:

LDLLDLreceptor

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 homozygousfor sickle-cell allele

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

Sickle-cell (abnormal) hemoglobin

Sickle cells

Breakdown ofred blood cells

Clumping of cellsand clogging of

small blood vessels

Accumulation ofsickled cells in spleen

Physicalweakness

Anemia Heartfailure

Pain andfever

Braindamage

Damage toother organs

Spleendamage

Impairedmental

functionParalysis Pneumonia

and otherinfections

Rheumatism Kidneyfailure

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

4. Polygenic inheritance

Phenotype of Hydrangea flower color

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

Non-genetic factors affecting phenotype: Environmental effects

Non-genetic factors affecting phenotype: Epigenetic factors

Gene expression is impacted by changes of chromatin structure through chemical modification

• 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 pattern of inheritance

Can be used to determine maternal lineage