Typ & Atyp - Week 5 - Genetics Intro

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What is Genetics?

http://www.genome.gov/Glossary/index.cfm

Three aspects:

Mollecular - is the field of biology and genetics that studies the structure and function of genes at a molecular level

Behavioural - is a field in which variation among individuals is separated into genetic versus environmental components

Population - is the study of genetic variation within populations, and involves the examination and modelling of changes in the frequencies of genes and alleles in populations over space and time

Gene: A

category of nucleic acid sequences that function as units of heredity and which

code for the basic instructions for the development, reproduction, and

maintenance of organisms

(In

the absence of demonstrated function a gene may be characterized by sequence,

transcription or homology)

Genome: All

the genetic material in the chromosomes of a particular organism

DNA makes RNA makes Protein

http://youtu.be/J3HVVi2k2No

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Genetic Variation

Beware the term mutation - sometimes means 'change' sometimes means 'disease instigating change'

Also the term polymorphism - can mean non disease causing change, or change found in the population at 1% or higher

Better to use terms: "sequence variant",

"alteration" and "allelic variant"

SNPs: Single Nucleotide

Polymorphism (~3x1015 )

A single nucleotide polymorphism, often abbreviated to SNP (pronounced snip; plural snips), is a variation in a single nucleotide that occurs at a specific position in the genome, where each variation is present to some appreciable degree within a population (e.g. >1%).

VNTR: Variable Number Tandem

Repeat (short repeating sequences,

usually 10's of bases) (1000s)

CNV: Copy Number Variation

(>1000 bases) (~0.12% of genome), often de-novo

A copy number variation (CNV) is when the number of copies of a particular gene varies from one individual to the next

Following the completion of the Human Genome Project, it became apparent that the genome experiences gains and losses of genetic material

Mobile elements within the genome

(Transposons)

(or transposable element) is a small piece of DNA that inserts itself into another place in the genome

Sequence variation is measured by:

PCR - (Polymerase Chain Reaction): one

variant at a time

Microarrays: millions of variants

at a time

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Animal Models

Common

model organisms

-

Mouse

- C.elegans (nematode worm)

-

Drosophila (fruitfly)

-

Zebrafish

Benefits of animal models: Short life span, simple phenotype, gene manipulations easy

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Genetic Engineering

Can use knockouts = selectively (using restriction enzymes) 'chop' that bit of the gene out

Mouse gene can also be replaced with a human gene using viral transfection

Two Main study designs:

Behavioral genetics - e.g. MZ twin studies

Genetic association studies

TWIN STUDIES

A:

Additive (genetic) variance (always 1 in MZ or .5 in DZ)

C:

Common (shared) environment (always 1)

E:

Non-shared environment (always 0)

MZ twins 100% DNA non identical 50%, so if a strong genetic component in a given phenotype you would expect both identical twins to have a high chance of presenting with that phenotype

GENETIC ASSOCIATION STUDIES

Include Phenotype / trait measures

Clinical diagnosis

Reminder: Few

variations at a time – uses PCR

Millions

of variations from across the genome at the same time (Genomewide association studies) – uses

Microarrays

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Human Models

Wide variety of human phenotypes

Not directly manipulable - and should not be ethically

Have to rely on natural experiments

Therefore, only analysed by:

–Behavioural

genetics (twin study design)

–Genetic

association studies