Outline

 Chromosomal theory of inheritance

 Chromosome segregate in reliable and a limited number of predictable ways
during meiosis
 Evidence that genes are on chromosomes
 Morgan: flies, genes on X chromosome
 Creighton & Mclintock? Maize geneticists, showed genes are on chromosomes,
and showed evidence for crossing over. Universal evidence
 Mendel introduced the idea of testcrosses
 Inheritance is particulate… what are these particles?

Status of our knowledge

 Selective breeding can change the phenotype of a species (ex: dogs)
 Both parents contribute to the phenotype of the offspring
 Evidence: recessive shows up in F2
 Mendel's dihybrid crosses where F1 has yellow from one parent, wrinkled
from the other
 Inheritance is particulate in nature (no blending)
 Evidence: recessive in F2
 Even true for snap dragon flower color, F2 would be 1:2:1 red:pink:white
 When the phenotype of parents differ, one trait is dominant other is recessive
 If parents differ in more than one trait, the traits will assort independently
 F2 dihybrid crosses make 9:3:3:1 ratio
 Gene is often named for the mutant or recessive trait
 Gene that confers red eyes in the flies is the white gene
 Yellow seeds is the green gene

Are hereditary determinants carried in the blood?

 Pangenesis: particles circulating in the body of the organism, collect in the gonads
and be transmitted to the organism.
 Perhaps it’s the blood → transfusion experiments
 Rabbit experiments: does the offspring look like phenotype of the recipient
animal or the phenotype of the animal that donated the blood?
 In all cases, looks like the phenotype of the recipient animal. Suggests
that these particles are not contained in the blood

Cell Theory: Schwann & Schleiden

 All organisms composed of cells, cells divide, nucleus, string like particles inside
nucleus, when nuclei divide these particles also divide
Weismann: Asymmetric inheritance of nuclear determinants (germ cells)
 Trying to answer why cells differentiate? (neuronal cell, skin cell etc)
 In nucleus there are different determinants
 Reproductive cells are germ cells separate from soma and only the information in
the soma is important for the offspring (germ plasm)
 Refutes Lamarckian inheritance

The Chromosomal Basis of Inheritance

Sutton: grasshoppers and spermatogenesis
 Boveri-sutton theory of chromosomal inheritance: showed that the theory of the
Mendelian laws of inheritance could be applied to chromosomes at the cellular
level
  Dissect out testes, see spermatogenesis (dividing of germ lines)
 Saw different stages of meiosis
Sutton’s explanation of Mendel’s results
Mendel's Observations Chromosomal Correlation
Particulate factors Genes on chromosomes
Two members of a gene pair Homologous chromosomes
segregate segregate during meiosis
Gene pairs assort independently Nonhomologus chromosomes
assort independently during
meiosis
 Consequences of genes being on chromosomes: if genes are on chromosomes
and there is a regular order to genes on chromosome, then some traits should
appear together.

Bateson, Punnett, Saunders

 Reported cases of genes being in coupling or repulsion
 Question: do the genes for flower color & pollen shape in peas assort
independently?
 Experiment: cross two strains homozygous for two different traits
 Purple flowers, long pollen x red flowers, round pollen
 F1: purple flowers, long pollen
 F2: not in 9:3:3:1 ratio, when you have too high parental class, it suggests
linkage. Purple and long pollen is linked while purple and round pollen is in
repulsion
Morgan: The gene is the fundamental unit of heredity?
 Drosophila w/ white eyes, mostly male flies
 Genes must reside on chromosomes and that each gene must reside on a
particular chromosome. The trait for eye color must be on a sex chromosome
 White gene missing on the & chromosome and red dominant on the X
 Sex determination in drosophila: the Y chromosome allows for spermatogenesis
but doesn’t determine sex. The ratio of X chromosomes to # of autosomal
chromosomes
 In humans, Y chromosome, SRY gene determines the male sex
 In drosophila, XX:AA=1 female, X:AA= 0.5 male
Species XX XY XXY X0
Drosophila F M F M-sterile
Human F M M-klinefelter F-Turner

Eye color in Drosophila

 Eye color is on the X chromosome, all males are hemizygotes
 Alternative hypothesis: maybe females just can’t have white eyes
 Test cross: females from F1 x white eyed males. Produces white eyed
females.
 Should be 1:1:1:1 but less white eyed flies because less viable, also affects
seratonin pathways.
 Evidence that genes are on chromosomes

Nondisjunction: proof for chromosome theory

  Nondisjunction: the failure of one or more pairs of homologous chromosomes or sister
chromatids to separate normally during nuclear division, usually resulting in an abnormal
distribution of chromosomes in the daughter nuclei.
 Female white eyed: w/w/Y
 Male, sterile: 0/+ (didn’t get a chromosome from mother at all, just wt X from father)
 Sister chromatids i/o separating properly, go into one cell
 xxx : not viable
 Xxy: female, viable
 X: male
 Y

 More convincing evidence

Experiments of Creighton & McClintock: genetics of kernel color in corn

 Supports that genes are on chromosomes and the physical and there's physical
and genetic exchange of material between chromosomes
 Mutant phenotype: colorless and waxy
 Colored starchy (heterozygous, dominant) : heterochromatic knob at the top of the
chromosome, translocation of chromosome 8 on chromosome 9 is also seen
 Colored starchy: In the absence of recombination it could make two different
gametes. Ones with recessive colorless and dominant waxy. And ones with
dominant colorless and recessive waxy.
 Colorless waxy: can only make one type of gamete. Recessive colorless with
recessive waxy.
 There's 4 different combinations but only two different phenotypes: colored and
waxy, and colorless and starchy.
 Only way to get colored starchy and colorless waxy, there would need physical
exchange of material b/w chromosomes
  Knob linked to dominant colorless allele and chromosome extension linked to
recessive waxy allele
 Cytogenetic proof (knob & extension) that chromosomes are exchange which are
correlated to traits
 Colored kernels had the heterochromatic knob
 Waxy got the chromosome 8 extension
These experiments showed that crossing over was the result of an exchange of
genetic information b/w homologous chromosomes
 If crossing over is the physical exchange of chromosomal material, then the
recombinant phenotypes should each contain one of the cytological
landmarks

Pedigree Analysis
 Rare disease traits would skip generations
 ** will ask what’s the prob that an individual is heterozygous
 ** deduce whether or not something is sex linked
There are no “disease” genes
 All genes are normally used by the organism. Each somatic cell contains 2 copies
of all autosomal genes. The function of genes can be impaired or modified by
mutations
 Mutant alleles are associated with the development of a particular diseased trait
 CF: cystic fibrosis transmembrane conductance regulator functions as a chloride
channel
 Genetically inherited diseases are rare. Affected individuals for a dominantly
inherited trait are usually heterozygous.
 Unless indicated otherwise, for recessively inherited diseases, most unrelated
individuals will not be carriers
Common traits in humans
 Dominant: tongue roller, free ear lobe, widow's peak, bent little finger
 Recessive: attached ear lobe, hitchiker's tumb
Hallmarks of recessively and dominantly inherited traits
 Autosomal recessive
 Parents unaffected
 Affected progeny are both females and males
 Phenotype is rare, often revealed by consanguineous unions
 Siblings share 1/2 of alleles, first cousins share 1/8 of their alleles
 Mendelian ratios are rarely observed in families bc sample size is small
 Autosomal dominant
 Phenotype occurs in every generation
 Affected parents transmit phenotype to both sons and daughters
 On average, half of the children should show phenotype
 X-linked dominant
 Affected female transmits to 50% male and female progeny
 Affected male transmits to 100% of daughters and 0% sons
 X-linked recessive
 Females are carriers, males are affected
 Carrier female will transmit to 50% of sons (affected) and 50% of daughters
(Carriers)
 *** review slides 47-end and answer the questions