The Chromosomal basis of Inheritance It’s where the genes are….

The Chromosomal Theory of Inheritance Genes have specific loci on chromosomes Chromosomes undergo segregation and independent assortment

Chromosomal Linkage Thomas Morgan XX (female) vs. XY (male) Worked with Drosophilia melanogaster XX (female) vs. XY (male) Some other organisms have a different system (link) Sex-linkage: genes located on a sex chromosome Animate! Linked genes: genes located on the same chromosome that tend to be inherited together

Genetic recombination Crossing over of linked genes- Now, if linked genes get separated during crossover, they DO assort independently of each other! Genetic maps The further apart 2 genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency. (Think of the likelihood of being on the same ride the further apart you are in line….) Linkage maps Genetic map based on recombination frequencies Animate!

Human sex-linkage SRY gene: gene on Y chromosome that triggers the development of testes Fathers= pass X-linked alleles to all daughters only (but not to sons) Mothers= pass X-linked alleles to both sons & daughters Sex-Linked Disorders: Color-blindness; Duchene muscular dystrophy (MD); hemophilia X-inactivation: 2nd X chromosome in females condenses into a Barr body (e.g., tortoiseshell gene gene in cats)

Chromosomal Alterations Non-disjunction: members of a pair of homologous chromosomes do not separate properly during meiosis I or sister chromatids fail to separate during meiosis II. Aneuploidy: abnormal number of a certain chromosome. Examples: Monosomy X ~ Turner Syndrome (only viable human monosomy) Trisomy 21~ Down Syndrome Trisomy 13 ~ Patau Syndrome Trisomy 18 ~Edward’s Syndrome Polyploidy: more than 2 complete sets of chromosomes. Comes from non-disjunction of all chromosomes Common in Plant Evolution.

Alterations in Chromosome Structure Can result from non-reciprocal crossovers or weak area of chromosomes. Deletion: removal of a chromosomal segment Duplication: repeats a chromosomal segment (a fragment may join a homolog) Inversion: segment reversal in a chromosome (reattaches in reverse) Translocation: movement of a chromosomal segment to another

Various effects of Chromosomal Alterations: -Homozygous deletions are usually lethal -Duplications & translocations usually deleted -Some reciprocal translocations can alter phenotype because of “POSITION EFFECT”: -The influence on a gene’s expression because of its location among neighboring genes.

Genomic imprinting Identical alleles may have different effects on offspring, depending on whether they arrive in the zygote via the ovum or via the sperm. “Something” happens to the gene after they arrive to form the zygote May involve degrees of methylization (CH3 groups) Example:Fragile X syndrome: higher prevalence of disorder and in males http://medgen.genetics.utah.edu/photographs/pages/fragile_x.htm

GENOMIC IMPRINTING Prader-Willi / Angelman Syndrome- Another example of GENOMIC IMPRINTING Prader-Willi / Angelman Syndrome- Both disorders are caused by a deletion on Chromosome 15 but: If the altered chromosome came from Dad: Prader-Willi- Mentally handicapped, short, obese http://medgen.genetics.utah.edu/photographs/pages/praderwilli.htm If the altered chromosome came from Mom: Angelman’s Syndrome- motor/mental symptoms, jerky, uncontrolled laughter http://medgen.genetics.utah.edu/photographs/pages/angelmann.htm

Most (but not all) Disorders are recessively Inherited. Defective alleles code for either a malfunctioning protein…. or no protein at all. Heterozygotes can be phenotypically normal if one of the normal copies is all that is needed. They are, of course, carriers. Most people with recessive disorders are born to “normal” parents. (carriers) Probability is ¼ that the mating of 2 carriers will produce a homozygous recessive. …and 2/3 that (s)he will be a carrier. Consanguinity: condition that results from shared ancestry Results in more homozygous recessives. (Stearns County Syndrome) REMEMBER!- not all disorders are recessive some are “late-acting” & occur after sexual maturity. Example- Huntington’s Disease

Some other Genetic disorders: Cri-du-Chat: A specific deletion in Chromosome 5 mentally handicapped, distorted face, cry that sounds like a cat Chronic Myologenous Leukemia- Portion of Chromosome 22 translocates with portion of chromosome 15 Patau Syndrome: Trisomy 13 Severely mentally handicapped, cleft lip http://medgen.genetics.utah.edu/photographs/pages/trisomy_13.htm Edward’s Syndrome: Trisomy 18 Low ears,deformed fingers, heart problems http://medgen.genetics.utah.edu/photographs/pages/trisomy_18.htm