Chapter 15 The Chromosomal Basis of Inheritance

Chromosome Theory of Inheritance Created by Sutton, Boveri, et al in 1902 States that Mendelian genes have specific loci on chromosomes, and it is the chromosomes that undergo segregation and independent assortment

Genes are Traced to Specific Chromosomes Thomas Hunt Morgan was the first to associate a specific gene with a specific chromosome, early in the 20 th century Experiments provided convincing evidence that chromosomes are indeed the location of Mendel’s heritable factors

Step One: Choose an Experimental Organism Used Drosophila, a type of fruit fly Chosen because a single mating will produce hundreds of offspring, and a new generation can be bred every two weeks Only has four pairs of chromosomes, which are easily distinguishable with a light microscope

Bred these flies for a year before a mutant phenotype had come about – The wild type has red eyes, where as the mutant had white – Found later that it is a Sex Linked gene (found only on X chromosome) Further supported the chromosome theory of inheritance

Some Genes Are Linked Morgan found that wing size and body color were linked genes found on the same chromosome – Instead of crosses showing Mendelian outcomes, they were either dominant or recessive, and hardly ever heterozygous

Recombination of Unlinked Parental types are offspring who share a phenotype with the parent generation Recombinants are offspring that do not share a phenotype with the parent generation – Blame it on recombination, not the mailman!

Recombination of Linked Genes Crossing over accounts for the recombination of linked genes Nonsister chromatids break and switch fragments – Allows for recombinants to show in linked genes as well

Genetic Map An ordered list of the genetic loci along a particular chromosome The recombination frequencies calculated reflect the distances between genes on a chromosome – The farther the two genes are apart, the more likely that crossover will occur between them and therefore the higher the recombination frequency Came up with a linkage map, a genetic map based on recombination frequencies Red Rover Example!

Practice Example

Practice Problem A-B = 78.9%, or 78.9 map units B-C = 1.7%, or 1.7 centimorgan A-C = 18.3%

Cytological Maps Locate genes with respect to chromosomal features, such as stained bands, that can be seen with a microscope – Linkage maps don’t actually paint a true picture, they give a rough idea of how a chromosome is aligned

Sex Chromosomes It is quite simple, in humans, if you receive two X chromosomes, then you are female, and if you receive one X and one Y, then you are male However, if you do get a Y chromosome, that does not mean you are male – SRY genes (sex determining region of Y) is required for the development of testes In the absence of SRY, ovaries develop

Bugs: there is the X-0 system – There is only 1 sex chromosome, if you receive two copies you are female, only one means you are male Birds, fish, and some insects: Z-W system – Female is what determines sex of offspring, males are ZZ, females are ZW Bees and Ants: haplo-diploid system – No sex chromosomes, females develop from fertilized ova and are diploid, males develop from unfertilized eggs and are haploid (they have no father)

Interesting Fact Sperm containing a Y chromosome are lighter, and therefore more likely to reach the target (egg) – At fertilization, there is a ~56% likelihood of a male being produced – However, most fertilizations don’t make it to pregnancy, (more often male than female) so the odds are still 50/50

Sex Linked Disorders Duchenne Muscular Dystrophy – One of 3,500 males – Rarely live past early 20’s – Progressive weakening of muscles and loss of coordination – Traced the disorder to the absence of a key muscle protein at a specific locus on the X chromosome

Hemophilia is the absence of one or more of the proteins required for blood clotting – Early Jewish people had an idea of how hemophilia was passed, and sons born to women with a family history of the disorder were exempt from circumcision – Passed along through Royal Families in Europe Consanguenios mating

X-Inactivation in Female Mammals One X is completely inactivated during embryonic development – It is random The inactive X in each cell of a female condenses into a compact object called a Barr body Females consist of a mosaic of two types of cells; those with the active X from mother, an those with the active X from father – Shown in a calico cat, which has an allele for orange and black – In humans, sometimes appears as a prevention of developing sweat glands Will have patches of normal skin and patches without sweat glands

Alterations to Chromosomes Change in number Change in structure

Change in Number Nondisjunction: the members of a pair of homologous chromosomes do not move apart properly during meiosis Some gametes will receive two of the same, and some will receive none – Zygote will have abnormal number of chromosomes, called aneuploidy

If a chromosome is present three times, it is called trisomy – 2n + 1 If a chromosome is missing, it is called monosomy – 2n – 1 Some organisms have more than two complete sets of chromosomes, they are called polyploidy – Common in plants

Change in Structure Deletion: a chromosomal fragment lacking a centromere is lost during cell division Insertion: fragment may become attached as an extra segment to a sister chromatid Inversion: reattaches in the reverse order Translocation: fragment joins a nonhomologous chromosome Duplication: just what the name says

Human Disorders- Numbers Most aneuploidy human zygotes are naturally aborted – Chromosome alterations are too disasterous Those who survive end up with disorders such as: – Down’s Syndrome – Klinefelter Syndrome – Turner Syndrome

Down Syndrome 1:700 Extra chromosome 21 (Trisomy 21) Characteristic facial features, short stature, heart defects, respiratory infections, mental retardation, more apt to have leukemia and Alzheimers Has a correlation to age of mother

Klinefelter Syndrome 1:2,000 births An extra X chromosome in males: XXY Have male sex organs, but testes are small and sterile Breast enlargement and other feminine body characteristics

Turner Syndrome 1:5,000 births Monosomy X Phenotypically female, sex organs do not mature, sterile

Human Disorder- Structure Genetics Library

Disorders that are from Mom or Dad Prader-Willi syndrome – Mental retardation, obesity, short stature, small hands and feet – Deletion on chromosome 15 from father Angelman syndrome – Spontaneous laughter, jerky movements, other motor and mental symptoms – Deletion on chromosome 15 from mother Genomic imprinting

Genomic Imprinting A gene on one chromosome is somehow silenced, while its allele on the homologous chromosome is left free to be expressed Same alleles may have different effects on offspring, depending on if they originated in the ovum or sperm – In offspring, all imprints are erased and gone for next generation Happens because of methyl groups – epigenetics

Amendment Not all genes are located on chromosomes, or even in the nucleus Extranuclear genes are found in mitochondria and chloroplasts – Tell them when to reproduce – Based on endosymbiotic theory Mitochondrial DNA comes from the mother because the mitochondria passed on by the zygote all come from the cytoplasm of the ovum