GeneticsGenetics

What is Genetics

• Species: a group of interbreeding populations

• Each species is unique because of its own set of traits

• These traits are passed on from generation to generation (heredity)

• Genetics is the scientific study of heredity.

Why is genetics important?

Health

GeneticsEnvironment

ISI Web of Science topic search for "genetic AND disease"

0

1000

2000

3000

4000

5000

6000

7000

800019

91

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

Nu

mb

er

of

jou

rna

l re

co

rds

Genetic knowledge used for thousand years in agriculture

Patterns of disease inheritance known for 1000s of years, e.g. haemophilia

Trait - a characteristic brought about by the expression of a gene or many genes

a. anatomical - height, nose shape b. chemical - eye color, blood type c. behavioral – tongue rolling, temperaments

How are traits inherited?

What is a gene?• A gene is a stretch of DNA whose sequence

determines the structure and function of a specific functional molecule (usually a protein)

DNA

Protein

…GAATTCTAATCTCCCTCTCAACCCTACAGTCACCCATTTGGTATATTAAAGATGTGTTGTCTACTGTCTAGTATCC…

Computer program

Specific function

…function sf(){document.f.q.focus()}…

Working copymRNA

DNAs are coiled as chromosomesin the nucleusof the cell

Karyotype

DNA(deoxyribonucleic acid)

mR

NA

Protein

Down syndrome karyotype (trisomy 21)

Mendel’s experiments

Mendel’s data

Mendel deduced the underlying principles of genetics from these patterns

1. Segregation

2. Dominance

3. Independent assortment

Mendel’s Law of Segregation

• A normal (somatic) cell has two variants (alleles) for a Mendelian trait.

• A gamete (sperm, egg, pollen, ovule) contains one allele, randomly chosen from the two somatic alleles.

• E.g. if you have one allele for brown eyes (B) and one for blue eyes (b), somatic cells have Bb and each gamete will carry one of B or b chosen randomly.

B b

B BB Bb

b Bb bbEggs

Sperm

Meiosis in a Nutshell

Meiosis is a special type of cell division that

occurs in sexually reproducing organisms.

It reduces the chromosome number by half,

enabling sexual recombination to occur.

It ensures that an organism has the same number

of chromosomes in each generation.

Terminology…

• Haploid: containing one copy of each chromosome (n=23)

B b

B BB Bb

b Bb bbEggs

Sperm

• Diploid: containing two copies of each chromosome

(2n=46)

Terminology…

• Genotype: the states of the two alleles at one or more locus associated with a trait

• Phenotype: the state of the observable trait

Genotype PhenotypeBB (homozygous) Brown eyes

Bb (heterozygous) Brown eyes

bb (homozygous) Blue eyes

Mendel’s Law of Dominance

• If your two alleles are different (heterozygous, e.g. Bb), the trait associated with only one of these will be visible (dominant) while the other will be hidden (recessive).

E.g. B is dominant,

b is recessive.B b

B BB Bb

b Bb bb

Eggs

Sperm

Mendel’s Law of Dominance

• If your two alleles are different (heterozygous, e.g. Bb), the trait associated with only one of these will be visible (dominant) while the other will be hidden (recessive).

E.g. B is dominant, b is recessive.

B b

B BB Bb

b Bb bbEggs

Sperm

Mendel’s Law of Independent Assortment

• Knowledge of which allele has been inherited at one locus gives no information on the allele has been inherited at the other locus

S/s Y/y

SY Sy sY sy

25% 25% 25% 25%

Mendel’s Law of Independent Assortment

S Y

s y

Gametophytes (gamete-producing cells)

S Y

s yGametes

A b

a BRecombinants

Segregation

Mendel’s Law of Independent Assortment

S Y

s y

Gametophytes(gamete-producing cells)

S Y

s yGametes

S y

s YRecombinants

Recombination

Segregation

• Simplified view of eye colour inheritance: bi-allelic Mendelian trait

– Brown dominant: BB, Bb

– Blue recessive: bb

Human eye colour

B b

B BB Bb

b Bb bbEggs

Sperm

Human eye colour

?

B?

B?B?B? bb

bb B?

BB, Bb (Brown, dominant) Bb (blue, recessive)

What are the possible eye colors of this child?

Non-Mendellian Inheritance : Non-Mendellian Inheritance : Incomplete DominanceIncomplete Dominance

• Some alleles for a gene are not completely dominant over the others. This results in partially masked phenotypes which are intermediate to the two extremes.

Non-Mendellian : Sex LinkageNon-Mendellian : Sex Linkage

• All chromosomes are homologous except on sex chromosomes.

• Sex chromosomes are either X or Y.• If an organism is XX, it is a female, if XY it is

male.• If a recessive allele exists on the X

chromosome. It will not have a corresponding allele on the Y chromosome, and will therefore always be expressed

Sex linkage exampleSex linkage example

• Recessive gene for white eye color located on the Xw chromosome of Drosophila.

• All Males which receive this gene during fertilization (50%) will express this.

• If a female receives the Xw chromosome. It will usually not be expressed since she carries an X chromosome with the normal gene

Human Sex LinkageHuman Sex Linkage

• Hemophilia:– Disorder of the blood

where clotting does not occur properly due to a faulty protein.

– Occurs on the X chromosome, and is recessive.

• Thus a vast majority of those affected are males.

– First known person known to carry the disorder was Queen Victoria of England. Thus all those affected are related to European royalty.

• Phenotypes are controlled by more than 1 allele. Eg. Blood types are regulated by 3 separate genes.

• ABO Blood typing– Humans have multiple types of surface antigens on RBC's – The nature of these surface proteins determines a person's

Blood Type.– There are 3 alleles which determine blood type IA, IB, or IO. This

is referred to as having multiple alleles– Human blood types are designated as A, B or O.

• Type A denotes having the A surface antigen, and is denoted by IA

• Type B denotes having the B surface antigen, and is denoted by IB

• Type O denotes having neither A or B surface antigen, and is denoted by IO

– There are several blood type combinations possible• A• B• AB (Universal recipient)• O (Universal donor)

Non-Mendellian : Multiple AllelesNon-Mendellian : Multiple Alleles

Non-Mendellian: Continuous VariationNon-Mendellian: Continuous Variation

• Many traits may have a wide range of continuous values. Eg. Human height can vary considerably. There are not just "tall" or "short" humans

Non-Mendelian: mtDNANon-Mendelian: mtDNA

Mitochondrial DNA point mutations are maternally inherited and can occur in rRNA or tRNA genes, or in genes coding for proteins of respiratory chain complexes.

Phenotypes associated with mtDNA mutations

• Longevity• Stroke• Seizures• Reduced sperm motility• Common migraine• Bipolar disorder• Exercise intolerance, fatigability

Non-MendellianNon-Mendellian

• Gene interaction: – Many biological pathways are governed by multiple

enzymes, involving multiple steps. If any one of these steps are altered. The end product of the pathway may be disrupted.

• Environmental effects:– Sometimes genes will not be fully expressed owing to

external factors. Example: Human height may not be fully expressed if individuals experience poor nutrition.

Summary

• Mendel deduced three simple laws of inheritance:– Segregation– Dominance– Random assortment

• The majority of traits don’t follow these rules but Mendel’s laws are nevertheless crucial to understanding almost all genetic inheritance

Statistical aside: Mendel’s data too good to be true?

Human Genome Project

• Sequenced almost all 3 billion DNA base pairs (2003)• Current work includes:

– ENCODE Project (ENCyclopedia Of DNA Elements) to characterise functional elements in genome

• 20,000-25,000 genes (1.5% of genome)• The bits in between (98.5% of genome)

– Characterise human DNA sequence variation• Find and describe DNA sequence variation (International

HapMap Project) • Find significance of sequence variation (e.g. contribution to

complex diseases)

• Post-genomic genetics has enormous promise for tracking down the genes involved in common complex diseases

• Currently our ability to exploit this potential is limited by– study size– difficulty of correcting for confounding factors

Must tutorials:

• http://learn.genetics.utah.edu/content/begin/tour/

CLICK all 4 topics under “BASICS”

TOUR THE BASICS

DNA TO PROTEIN

HEREDITY & TRAITS

AMAZING CELLS