Genetics in life, love and lab

Spontaneous mutation at low levels is normal

Fly homeotic (Hox) selector gene mutations : cool

Antp

Ubx

Antennapedia

UltrabithoraxLoss-of-function (lof)

Mutated gene DNA, modified fly

proboscipedia

Ultrabithorax

What is DNA, Stephen?

Chromatin

From: Felsenfeld et al., 2003

 open 

 closed 

1 m

1 µm

A

a

A

aA

a

A

a

2n4n

2 x 2n

Mitosis: one mother cell becomes two daughter cells

2 x ‘2n’

A

a

2n

A

a

4n

a

A

A

A

a

a

4 x 1n (gametes)

Meiosis: one mother cell becomes four gametes

DNA double helix

A T A G G G C C T C A C A CA G C A T

T A

4 building blocks: A, T, G, C

A T A G G G C C T C A C A CA C A G C A T

T A T C C C G G A G T G T G T G T C G T A

Mutations e.g. stutteringDNA polymerase

2 x 2n

A

a

A

a

2n

A

a

4n

A

a

16 x 2n

256 x 2n

Incomplete mitoses give giant chromosomes

Giant chromosomes of Drosophila and cytogenetics

We can see rearrangements such as inversion loops

Amniocentesis, A pre-natal test for high-risk pregnancies

A karyotype for a human cell (e.g. amniocentesis)

Trisomy for chromosome 21

Protein

Gene functio

n

A Cystic Fibrosis (mucoviscidose)-bearing family tree

I

II

III

IV

The family tree The family tree reveals the reveals the recessiverecessive nature nature of the disease of the disease

The disease The disease appears in the appears in the offspring of offspring of two apparently two apparently healthy healthy individualsindividuals

Two sick childrenTwo sick children

A quick detour concerning positional cloning

.

six genotypes (AA, AO, BB, BO, AB, & OO) &

four phenotypes (A, B, AB, O)

As a function of which protein form – A, B, A and B, or neither of these – is expressed 

A B O

A marriage between AB and O parents

A B x O O

½ A ½ B

O ½ AO (A) ½ BO (B)

Frequency of I - locus alleles

Allele IA IB  IO

Frequency 0.4 0.1 0.5

 

Frequency of ABO blood types

Phenotype A B AB O

Genotypes IAIA & IAIO IBIB & IBIO IAIB IOIO

Frequency 0.56 0.11 0.08 0.25

But in a population…

Frequencies of MN blood types

  MM MN NN f (M) f (N)

US Whites

0.29 0.50 0.21 0.54 0.46

Now for a different blood type marker:

Frequency of MN blood types

  MM MN NN f (M) f (N)

US White

0.29 0.50 0.21 0.54 0.46

                  Product Rule: probability of two events occurring together is the product of their separate probabilites

                So, the probability of AB and N blood types  =  f(AB) x f(NN) = (0.08) x (0.21) = 0.0168 (<2%)

Phenotype A B AB O

Genotypes IAIA & IAIO IBIB & IBIO IAIB IOIO

Frequency 0.56 0.11 0.08 0.25

The Experts…

A T A G G G C C T C A C A CA C A G C A T

A T A G G G C C T C A C A CA G C A T

A T A G G G C C T C A C A CA C A C A G C A T

A T A G G G C C T C A C A CA C A C A C A G C A T

0.31

0.32

0.14

0.23

Allele / DNA variant Allele frequency

The Experts always get their man !

Jumping genes

Normal instability:

Mirabilis jalapa

Transposable elements interrupt the chromosome and jump around

Bad genes run in families

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Los Angeles

Incidence of a genetically transmissible syndrome: LA

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Tokyo

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Incidence of a genetically transmissible syndrome: Tokyo

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Incidence of a genetically transmissible syndrome:

Iceland

A Cystic Fibrosis (mucoviscidose)-bearing family tree

I

II

III

IV

The family tree The family tree reveals the reveals the recessive nature recessive nature of the disease of the disease

The disease The disease appears in the appears in the offspring of offspring of two apparently two apparently healthy healthy individualsindividuals

Two sick childrenTwo sick children

In this family, the affected children come from a marriage between two first cousins, each of whom is a carrier.

‘Blood’ marriage

Homozygosis makes for bad blood

Victoria of England Nicolas II and Alexandra of Russia

Rasputin

Intermission