25 - Deviation from Hardy-Weinberg Equilibrium, Notas de estudo de Genética

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Deviation

from

Hardy

Weinberg

Equilibrium:

Wahlund

Effect

Real

data:

Navajo

populations

MN

blood

type

in

Navajo

MM:

MN:

NN:

Real data: Aborigine populations

MN

blood

type

in

Aborigine

MM:

MN:

NN:

Real data: Aborigine populations

MN

blood

type

in

Aborigine

MM:

p(M)

MN:

q(N)

NN:

TOTAL:

HW

Predicted: MM

MN

Very close to

HW

NN

Real

data:

Mixed

population

MN

blood

type

MM:

p(M)

MN:

q(N)

NN:

TOTAL:

HW

Predicted: MM

MN

NOT

close to

HW

NN

Random

mating

assumption

Any

two

individuals

as

likely

to

breed

as

any

other

two

individuals

Is

a

Navajo

lady

as

likely

to

breed

with

an

Aborigine

as

she

is

with

another

Navajo???

NO!

Hardy

Weinberg

assumption

VIOLATED!

Hardy

Weinberg

assumption

not

rejected:

Within Navajo

Within Aborigine

Deviation

from

HW

observed

in

combination

Result of

non

random mating

Observations:

Too few heterozygotes

Expected:

1. Observed:

Wahlund effect ‐^ sampling across populations gives underrepresentation of heterozygotes relative to HW

Why

does

it

matter???

First

step

in

genome

wide

association

studies

of

genetic

diseases

is

usually

to

test

for

HW

Why?

Example:

Imagine

Population

all

AA

Imagine

Population

all

aa

If

disease

is

more

abundant

in

Population

than

Population

Would say “ AA ” more likely to have disease than “ aa ” - “ Fake ” LD between disease and gene A - Disease gene may be on different chromosome than A, or disease maybe not even influenced by genetics at all!

Punchline

If

there

are

allele

frequency

differences

between

populations

at

a

SNP

If

there

are

disease

incidence

differences

between

those

populations

too

THEN,

it’ll

(erroneously)

look

like

a

gene

near

the

SNP

causes/

contributes

to

the

disease

Testing

for

HW

helps

you

avoid

this

error

Identifies if looking at one or more

populations

Real example where HW test WAS done but interpreted incorrectly…

study

of

BRCA

variants

Newborn males from hospital in United Kingdom

AA:

Aa:

aa:

Calculate

HW

expectations. Speculate on fit or lack of fit.

Real example where HW test WAS done but interpreted incorrectly…

study

of

BRCA

variants

Newborn males from hospital in United Kingdom

AA:

A:

a:

Aa:

HW

Expected

aa:

AA:

TOTAL:

Aa:

Deviation from

HW

aa:

statistically significant… too few Aa observed. Authors inferred Aa are less healthy than

AA

or aa.

Image

Credits,

Unit

Aborigines, © 2007 Mombas, CC by ‐ SA 3.0, en.wikipedia.org - Cupid, © Anna Velichkovsky, all rights reserved, www.photoxpress.com - Green DNA w/ red mutation, © appler, all rights reserved, www.photoxpress.com - Microarray, © 2006 Schutz, CC by ‐SA 3.0, en.wikipedia.org. - Crowd, © 2006 SchuminWeb, CC by ‐ SA 2.5, en.wikipedia.org - United Kingdom map, © 2006 Captain Blood, CC by ‐ SA 3.0, en.wikipedia.org - Pink ribbon, © 2007 MesserWoland, CC by ‐SA 3.0, en.wikipedia.org.