Genes, Chromosomes, and Human Genetics
11.1 Genetic Linkage and Recombination
Genes located on the same chromosome may be inherited together in genetic
crosses – they do not assort independently – because the chromosome is inherited
Linked genes – genes on the same chromosome
Linkage – the phenomenon of genes being located on the same chromosome
11.1a The Principles of Linkage and Recombination Were Determined with
Thomas H. Morgan: used the fruit fly (Drosophila melanogaster) to investigate
Mendel’s principles in animals.
Alfred Sturtevant: developed insight that resulted in the construction of the first
genetic map showing the relative order of genes on a chromosome and estimated
the distance separating the genes.
Made using the process of recombination (detectable) occurring on the space
separating 2 genes on the chromosomes paired during meiosis
far apart = more likely to be separated during meiotic crossing-over
Morgan’s Genetic Symbolism used to understand the crosses.
Normal or Wild-type genotype – a mutant
mutant alleles – based on the altered phenotype of the organism that expresses
wild-type allele – superscripted + sing (Antp )
dominant mutant – first letter in uppercase (Antp)
recessive mutant – first letter in lowercase (v)
Morgan – true breeding fruit flies with normal red eyes and normal wing length
(genotype pr , pr , vg , vg ) + a true breeding fly with recessive trait of purple
eyes and vestigial (short and crumpled) wings (genotype p+pr vgvg+
F1(wild-type female + double mutant male) – dihybrid (pr , pr, vg , vg) and
because of the dominant wild-type alleles they all ha red eyes and normal wings
F2(F 1ild-type dihybrid females + homozygous recessive males (test cross
parent)) – 2 types of progeny were higher and 2 were lower than 700/2800 for the
NO Mendel’s principle of independent assortment, which predicts 4 classes of
phenotypes in the offspring due to the fact that purple and vestigial genes were
carried on different chromosomes.
Non-Mendelian distribution because Morgan:
2 genes are linked genetically – physically associated on the same chromosome –
pr and vg are linked genes.
Chromosome recombination during meiosis -> behaviour of linked genes Frequency of recombination = distance between linked genes
2 parental gametes pr vg and pr vg generated by simple segregation of the
chromosomes during meiosis without recombination (crossing over) between the
genes + +
2 recombinant gametes pr vg and pr vg generated by recombination between the
homologous chromatids when they are paired in prophase I of meiosis
offspring of cross: produced by fusion of each of these 4 gametes with a pr vg
gamete produced by the prpr vgvg male parent.
Phenotypes of offspring = genotypes of gametes produced by dihybrid parents
“parental” – refers to genotype not phenotype – these are the ones that inherit
chromosome that were NOT involved in recombination in the dihybrid parent
Morgan: relative frequency of recombinant progeny = measure of distance
Eg. Purple eyes and vestigial wings on the same chromosome and are separated
by a recombinant offspring frequency distance of 10.7%
11.b Recombination Frequency Can Be Used to Map Chromosomes
Recombinant offspring frequency was characteristic of the 2 particular genes
involved and varied from less than 1% up to a maximum of 50%
variation in recombinant offspring frequencies used to map genes on
Linkage map – map of a chromosome showing the relative locations of genes
based on recombination frequencies
Eg. Genes a-b 9.6%, a-c 8%, c-b 2%
it doesn’t sum up because genes farther apart on a chromosome = more likely to
have more than one crossover between them.
single crossover - between 2 genes gives recombinant chromatids.
double crossover (2 single crossovers occurring in the same meiosis) - between 2
genes give the parental arrangement of alleles and is undetectable a-b
A C B
Created the first linkage map: arrangement of 6 genes on the Drosophila X
Map unit (mu) AKA centimorgan– unit of a linkage map = to a recombinant
offspring frequency of 1%
NOT absolute physical distances, IT IS relative, showing positions of genes with
respect to each other because the frequency of crossing-over giving rise to
recombinant offspring varies from one position to another along chromosomes 11.1c Widely Separated Linked Genes Assort Independently
Genes can be widely separated on a chromosome that recombination is almost
certain to occur at some point between them in every cell undergoing meiosis.
Then, genes assort independently even though they are on the same chromosome.
The map distance separating them will be 50 mu (50% recombinant offspring and
50% of recombinant offspring observed when genes are on different
Recombination event in a cell creates 2 recombinant and 2 nonrecombinant
Eg. 100 meiocytes going through meiosis = 400 gametes yield.
2 genes in 10 of the cells = 20 recombinant chromatids produced in prophase I
20 gametes would receive recombinant chromosomes and 20/400 =5% of the total
testcross progeny would be recombinant.
They would be 5 mu apart
Assume recombination event occurs along the chromosome in the space
separating the 2 genes in every one of the 100 cells going through meiosis
Result: 200 /400 = 50% recombinants = 50 mu separating the genes
Linkage between widely separated genes can still be detected by testing their
linkage to genes that lie between them.
Eg. A-b 23 mu, b-c 34%, a-c 57%
A-C genes that are located so far apart that they assort independently and show no
linkage since a cross over occur.
57 mu and 57% recombinant offspring frequency would not be seen because the
maximum frequency of recombinant chromatids is 50%.
Eg. Mendel’s flower colour and seed colour
11.2 Sex-Linked Genes
Sex-linked genes – gene located on a sex chromosome
pairs of chromosomes are different in both sexes because sex-linked genes are
Autosomes – chromosome other than the sex chromosomes
Genes on autosomes are the same patterns of inheritance for both sexes.
11.2a Females are XX and Males are XY in Both Humans and Fruit Flies
Species with sex chromosomes:
Females: 2 X chromosomes
Gametes = X chromosome
Sperm cell carries X chromosome and fertilizes an X bearing egg cell = XX.
Males: one X and Y chromosome
Y chromosome has short region of homology with the X chromosome pair
Gametes = half X and Y chromosome
sperm cell carries Y chromosome and fertilizes an X bearing egg cell = XY.
Punnett Square shows that fertilization is expected to produce females and males
with an equal probability of ½. SAME as drosophila. Other sex combinations been found: insects XO males (no Y chromosomes),
birds/butterflies/reptiles males have ZZ instead of XX and females are
11.2b Human Sex Determination Depends of the SRY Gene
One gene carried on the Y chromosome; SRY (sex determining region of the Y)
appears to be the master switch that leads to male at an early point in embryonic
1 month: rudimentary structures reproductive organs and tissues are the same
in XX and XY embryos
After 6-8 weeks:
XY embryos: SRY gene becomes active, producing a protein that regulates the
expression of other genes, stimulating part of these structures to develop the
testes. Tissues degenerate that would otherwise form female genitals; the
remaining form the male genitals.
XX embryos: NO SRY gene, development proceeds toward female reproductive
structures. Rudimentary male structures degenerate in XX embryos because the
hormones released by the developing testes in XY embryo are not present.
X and Y chromosomes are sex chromosomes, but only a few genes they carry
have any influence on sex determination or sexual function.
Most of the 2400 known genes on X chromosome code for phenotypes needed for
Genes governing structures needed by one sex are coded on autosomes.
Eg. Males inherit genes needed for uterine development and pass them onto the
offspring to be used by daughters – genes NOT expressed. Females have genes
for penis structure, by do not express them.
11.2c Sex-Linked Genes Were First Discovered in Drosophila
Males and females have different sets of sex chromosomes; the genes carried on
these chromosomes can be inherited in a non-Mendelian pattern called sex
Se Linkage arises from 2 differences between males and females:
- Males have 1 X chromosome, females have 2 X chromosomes
- Males have 1 Y chromosome, females have no Y chromosomes
Morgan discovered sex-linked genes and their pattern of sex linkage
Cross of white-eyed male with true-breeding red-eyed female
F : all red-eyed
White-eye is recessive
F2(F1interbreed): all 2 females had red eyes, half of2F males had red eyes and
half had white eyes
NOT Mendel’s principles expectation that both male and female F flies would
show a 3:1 ratio of red-eyed flies to white-eyed flies
Hypothesized: the alleles segregating in the cross were of a gene located on the X
chromosome –sex-linked gene
White-eyed male parent in the cross had the genotype X Y
X – X chromosome with a white allele and no allele on W+ W
Red-eyed female parent in the cross had the genotype X X Phenotype is red – dominance of XW+
F 2 Males are halW+X Y (red eyes) and W+lf X W (white eyes). Females are all
red eyed; father X and mother either X or X
Reciprocal cross – phenotypes were switched between parents
W W W+
White eyed female (X X ) anW red eyW+ male (X Y)
F 1 males had white eyes (X Y) – X from mother. Females had red eyes all
heterozygous (X W+X )
F 2 male and females showed a 1:1 ratio of red and white eyes
Key indicator of sex linkage is when all male offspring of a cross between a true-
breeding mutant female and a wild-type male have the mutant phenotype – since
male receives X chromosome from the female parent
11.d Sex Linked Genes in Humans Are Inherited as They Are in Drosophila
Pedigree – a summarized chart showing all parents and offspring for as many
generations as possible, the sex of individuals in the different generation, and the
presence or absence of the trait of interest.
Solid circle / square = presence of the trait
Humans & fruit flies
Sex-linked recessive traits appear more frequently among males than females
because males need to receive only one of the allele on the X chromosome
inherited from their mothers to develop the trait. Females need two copies of the
recessive allele, one from each parent, to express the trait.
Males are bleeders if they receive an X chromosome that carries the recessive
Develops in females with the recessive allele on both of their X chromosomes-
11.2e Inactivation of One X Chromosome Evens out Gene Effects
Mammalian females have twice as many copies of genes carried on the X
chromosomes as males, BUT they don’t require twice as much of the products of
Products from genes on the X chromosome could be equalized in both sexes if:
One X of female is “turned off” this one is USED in body cells in nature
Inactivation occurs by a condensation process – folds and packs the chromatin of
an X chromosome into a tightly coiled state
seen as Barr body – dense mass of chromatin
Inactivation occurs during