5.1 When Gene Expression Appears to Alter Mendelian Ratios
1. A number of factors can appear to disrupt Mendelian ratios.

Lethal Allele Combinations
1. A genotype that causes death before the individual can reproduce is called lethal.
2. Homozygous recessive lethal alleles eliminate a progeny class from the expected results of a cross.

Multiple Alleles
1. A gene can have more than two alleles, but a diploid individual only has one or two of them.
2. Phenylketonuria has over 300 identified alleles, cystic fibrosis has 1000+ known alleles.
3. Different allele combinations can produce different phenotypes and different severities of symptoms.

Different Dominance Relationships
1. Incomplete dominance of an allele produces a phenotype in the heterozygote that is intermediate between that of either homozygote.
2. Familial hypercholesterolemia is an example of incomplete dominance in humans.
3. Codominant alleles are both expressed in a heterozygote.
4. ABO blood groups are examples of a codominant trait in humans.

Epistasis-When One Gene Affects Another's Expression
1. In epistasis, one gene masks the effect of another. An example of epistasis in humans is the Bombay phenotype.
2. The Bombay phenotype results in O type blood for individuals homozygous recessive for the recessive "h" allele.

Penetrance and Expressivity
1. Genotypes vary in penetrance (percent of individuals affected) and expressivity (severity of symptoms).
2. Penetrance and variable expression are not well understood biochemically and are probably due to the complex biochemical environment all genes function in.
3. Polydactyly in humans displays variable penetrance and expressivity.

Pleiotropy-One Gene, Many Effects
1. A gene with more than one phenotypic effect is pleiotropic.
2. Porphyria variegata is an autosomal dominant disease that is pleiotropic.
3. Pleiotropy occurs when a single protein affects different body parts or is involved in multiple biochemical reactions.

Phenocopies-When It's Not in the Genes
1. A trait caused by the environment but resembling a genetic trait or occurring in certain family members is a phenocopy.

Genetic Heterogeneity-More than One Way to Inherit a Trait
1. Genetic heterogeneity occurs when different genes (or alleles) cause the same phenotype.
2. Heterogeneity occurs when genes encode different enzymes that are involved in the same biochemical pathway.

The Human Genome Sequence Adds Perspective
1. Knowing the DNA sequence of a protein-encoding gene increases identification of alleles.
2. DNA microarrays are useful in studying gene expression and epistatic interactions.

5.2 Maternal Inheritance and Mitochondrial Genes
1. Only females transmit mitochondrial genes, in the oocyte cytoplasm. In maternal inheritance, a trait passes from females to offspring of both sexes, but not from males.
2. Mitochondrial DNA does not cross over, mutates faster than nuclear DNA, and is present in many copies per cell.

Mitochondrial Disorders
1. A variety of disorders, collectively called mitochondrial myopathies result from mutations in mitochondrial genes. These generally cause muscle weakness and fatigue.
2. Ooplasmic transfer has been used to overcome mitochondrial disease in children conceived in vitro.

Heteroplasmy Complicates Mitochondrial Inheritance
1. In heteroplasmy, a mutation is present in some mitochondria only.
2. Causes variable expressivity.

Mitochondrial DNA Studies Clarify the Past
1. Mitochondrial DNA can be used for forensic pedigree and phylogenetic analysis.

5.3 Linkage
1. Linkage is the transmission of genes on the same chromosome.

Linkage Was Discovered In Pea Plants
1. Linkage was discovered in peas when a dihybrid cross did not show a typical 9:3:3:1 ratio, but had an excess of parental types.
2. Genes on the same chromosome are linked, and have different patterns of inheritance than the unlinked genes Mendel observed.
3. The farther apart two genes are on a chromosome, the greater the probability that crossing over will occur between them.
4. Genes that are combined by crossing over are called recombinant.

Linkage Maps
1. Genetic linkage maps are based on the observation that the likelihood of a crossover between two linked genes is directly proportional to the distance between them.
2. Linkage maps are built by tracking transmission of two traits at a time, and then determining the percent recombination between them.
3. First linkage maps were constructed by Alfred Sturtevant in 1911.

Linked Genes in Humans
1. Linkage data from pooled human pedigrees can be used to develop a human linkage map.
2. Linkage idsequilibrium (LD) in the human genome reveals non-randomly distributed sequences where recombination occurs infrequently.

The Evolution of Gene Mapping
1. Computer analysis of linkage data allows the computation of a LOD score (logarithm of the odds). A LOD score of 3 or greater signifies linkage between markers.
2. Haplotypes are a tightly linked series of markers that appear to be inherited as a single unit.
3. Markers may be protein coding alleles, variable restriction sites (RFLPs), variable short repeated sequences (VNTRs), or single nucleotide polymorphisms (SNPs).