Text description - Gene Mapping video

VISION: Glasshouse, peas, Mendel pic, peas in hand and gfx

NARRATOR: In 1856, an Augustinian friar began experiments on pea plants in the Abbey's greenhouse. His discoveries came to be known as Mendel's laws of heredity, and the man himself Gregor Johann Mendel, became known as the father of genetics.

VISION: Green and yellow pea seeds; Mendel GRAPHIC OF y/y,y/g,g/y

NARRATOR: By using simple probability models, Mendel showed the power of statistics and mathematics in genetics.He crossed pea plants producing only yellow seeds with plants producing only green seeds. The first generation hybrid seeds were all yellow. He then crossed those seeds and the second generation were 75% yellow and 25% green.

VISION: Allele diagram

NARRATOR: Mendel showed that each plant carries a pair of hereditary factors for each character, one factor from each parent. factor is dominant and one recessive. In this case the F1 seeds (yg) are phenotypically yellow and dominant. Mendel's two factors are forms of a single gene and we call them alleles of the single gene.

VISION: Hair, eyes..

NARRATOR: A blueprint of genes an individual carries is called a genotype. The expressed character of an individual is called a phenotype. Common examples are human hair colour, eye colour and blood types.

VISION: Blood types, graphic

NARRATOR: The familiar ABO blood system is an interesting genetic model in itself because there are three different allelles basically, the A, B and O allelle. The A and the B allelle are equally dominant and the O is recessive.

VISION: Melanie walks down WEHI corridor

I’m Melanie Bahlo, I’m a laboratory head at the Walter and Eliza Hall Institute biomedical research institute in Australia. I have a PhD in Statistics. I work a lot on genetic mapping, finding genes that cause disease in humans but I’ve done quite a lot of work in mouse genetics as well like for example, genes that determine coat colour in mice.

VISION: Melanie at her desk with slide on computer screen; Mice... WHITE and BLACK

Melanie Bahlo: The mice that we’re crossing here is a white mouse and a black mouse. Now even though we’ve just got two coat colours there, what is actually hidden in this cross are three colours and that’s because of the two genes that are involved and they're on different chromosomes and these two give the genetic information that determines the coat colour in this particular cross.

VISION: Vial of mouse blood; diagram of Loci.

NARRATOR: To work at the genetic level, they used mouse blood samples. In genetics, a locus (plural loci) is the specific location of a gene or DNA sequence on a chromosome. A list of loci in a known order separated by known genetic distances is called a genetic map.

VISION: Melanie at her desk with slide on computer screen; Punnett square slide

Melanie Bahlo: For each parent of course you get 2 alleles, one from one locus and one from the other locus, so that means that you can get 4 by 4 different genotypic combinations or allellic combinations and that will determine the outcome of the coat colour and that’s most easily explained in a Punnett square which is a very typical way of writing out the genetic combinations of allelles.

VISION: Melanie at her desk with slide on computer screen

Melanie Bahlo: if you have two copies of the capital A allele, that’s the agouti allele, you will be agouti, the browny colour and if you've got two copies of the capital C allele which is the wild type allele at the albino locus then you will not be albino. Albino is recessive, so you need two copies of the little c allele to make you white, and then the complication is that the albino locus masks whatever is going on at the agouti locus. So therefore it whites out everything if the mouse is albino. Now considering all the possible matings between the male and female mouse you have 16 different outcomes.

VISION: Melanie at her desk with slide on computer screen

Melanie Bahlo: in the top left hand corner you’ve got a double dose of the agouti allelle, the white type allele, at the agouti locus and a double dose of the c allele the wild type allele at the albino locus. So therefore the mouse is agouti and not albino.

VISION: Melanie at her desk with slide on computer screen

Melanie Bahlo: In contrast the albino mouse as you can see is actually capital A capital A which would be agouti if you could see it but because they're little c little c, they're albino and therefore that masks the agouti or black colour whatever it is. So it's brown underneath but you never see it because its masked by the albino allele.

VISION: Melanie at her desk with slide on computer screen; SLIDE OF F2; 3 different mice colours

Melanie Bahlo: So mating the black and the white mouse together produces a brown agouti. Then when you get to the F2 which is what's called an inter-cross so here you're mating the brothers and sisters offspring the F1s so all the agouti mice with each other you can now see the entire phenotypic spectrum: black, white and agouti mice and what's important here is the ratio which we've worked out from our Punnett square of the outcomes of these coat colours, considering the 16 outcomes is 9 to 3 to 4 of agouti to black to albino and that’s the first bit of maths down there.

VISION: graphic of chromosome

NARRATOR: A genetic marker is a variable locus in the DNA sequence with a known location on a chromosome.

VISION: Melanie at her desk with slide on computer screen

Melanie Bahlo: So here you can see a map of 156 genetic markers, so at each location we get a genotype for that marker. And the aim of the game is to correlate the genetic outcomes of the genetic markers with the coat colour expressions in terms of mathematics.

VISION: Melanie walks into Aust Genome Res Fac ; Extracting DNA in lab

Melanie Bahlo: All the chromosomes are now stacked up one after each other we've added them together so we’re basically scanning the genome for whats called linkage between the coat colour trait here and the genetic marker loci. On the white axis is our statistical measure here called the LOD score. A LOD score of about three is considered statistically significant and you can see that we've identified two coat colour loci so we were easily able to map the agouti locus to chromosome 2 where we know it resides and similarly the albino locus to chromosome 7 where we also know it resides.

VISION: Melanie walks out of Aust Genome Res Fac ; down WEHI corridor

Melanie Bahlo: So maths and stats are incredibly vital in genetics. In my particular area we’re assessing relationship between traits. We’re interested in identifying diseases running in families and the methodology that I've displayed here with regards to identifying the loci for the coat colours that’s exactly the same methods that we use, the mathematical machinery is the same, so we use this technique all the time and it’s a very powerful technique.