HUMAN GENETICS

TOPICS eligible to be covered by Exam 2

1.   Complex inheritance

1.1. Different types of dominance

1.1.1.  Complete dominance

1.1.2.  Semidominance

1.1.3.   Codominance

1.1.4.  Additive alleles

1.2. Multiple alleles

1.2.1.   Example ABO Blood types

1.2.2.  Skill: know how to predict/infer genotypes/phenotypes and their probabilities in pedigrees or crosses when allele interactions are completely, semi- or co-dominant.

1.3. Epistasis (e.g. coat color genes in mice)

1.4. Polygenic inheritance: many genes per trait

1.5. Pleiotropy: many traits per gene

1.6. Multiple factors shape phenotypes (e.g. genotype x environment)

1.7. Cytoplasmic inheritance ("maternal-effect" inheritance)

2.   Quantitative inheritance

2.1. Additivity of allele and gene interactions

2.1.1.  Additivity of gene as well as allele interactions

2.1.2.   Know how to predict/infer genotypes/phenotypes and their probabilities in pedigrees when allele and gene interactions are additive

2.1.3.  Threshold effect (e.g. risk can be treated as a quantitative trait!)

2.2. Gene-environment interactions affect phenotypes

2.2.1.   Define heritability (VG/VP ; VG+VE=VP) (How would you put this in words?)

2.2.2.   Heritability and the Breeder's Equation (R = h2S)

2.2.3.  The degree of heritability affects the strength of selection

2.2.4.  Skill: know how to predict the response due to selection, given the heritability of a particular phenotype (i.e. how to use the Breeder's equation)

3.   Central Dogma of Molecular Biology: Transcription

3.1. DNA is the central repository of inherited information

3.2. Inheritance occurs by DNA replication

3.3. This information is "transcribed" and "spliced" into mRNA (messenger RNA)

3.3.1.  Skill: know how to predict the transcript sequence given the coding or template strands of DNA

3.3.2.  Transcription occurs in nucleus

3.3.3.  The primary transcript. is processed:

3.3.3.1.     5' cap is added

3.3.3.2.     3' Poly-A tail is added

3.3.3.3.      Introns are spliced out, leaving Exons in the mature mRNA

3.3.3.3.1.        Protein coding sequences are within the Exons

3.3.3.4.     Alternative splicing allows multiple protein products to be made from the same gene

4.   Central Dogma of Molecular Biology: Translation

4.1. The nucleotide language of mRNA is "translated" into the amino acid language of proteins using ribosomes and tRNA (transfer-RNA)

4.1.1.  Translation occurs in the cytoplasm

4.1.2.   Different tRNAs have different Anticodons, antiparallel and complementary to the triplet Codons in the mRNA.

4.1.3.   Each tRNA is specific to not only its anticodon, but also to the amino acid

attached to it. tRNAs are thus the key to translation between nucleotide codons and amino acids

4.1.4.  Skill: know how to match codons to tRNA anticodons; know how to use the

Genetic Code table to predict the polypeptide encoded by a mRNA or coding strand of DNA (a Genetic Code table will be provided--do not memorize this!).

4.2. Proteins are "folded", possibly modified chemically, and transported within the cell (or secreted)

4.2.1.  Self-assembly (resulting from chemical properties of individual amino acids)

results in multi-protein complexes that provide functionality to the cell. The 3-dimensional shape of a protein (related to its function) is thus determined in large part by the 1-dimensional sequence of amino acids in the polypeptide

4.3. Mutations in DNA can result in changes to the encoded proteins...and thus to the phenotype

4.3.1.  Skill: know how to infer changes in the polypeptide sequence due to mutations occurring in the DNA (and vice versa)

5.   From genes to phenotype: Metabolic/enzymatic pathways

5.1. Enzymes are proteins that catalyze reactions

5.1.1.   Mutations can identify the functions of enzymes

5.2. Metabolic pathways are chained enzymatic reactions

5.2.1.   Mutations can help elucidate the order of these reactions

5.2.2.  Skill: know how to use the logic of the Beadle & Tatum experiment to infer the order of steps in an enzymatic pathway

5.3. Genes are regulated at many levels to ensure precision in the phenotype

6.   Population variation in traits is due at least partly to variation in genes

6.1. Other types of mutations in the human genome: Transposable elements & STRs

6.2. How to detect mutations

6.2.1.   PCR and gel electrophoresis

6.2.2.  Skill: know how to design a PCR experiment to test for STR variation; know how to predict sizes of PCR fragments and what the gel electrophoresis results should look like

6.3. How to identify ("map") genes responsible for traits

6.3.1.  GWAS (Genome-Wide Association Studies)

6.3.2.  Skill: know how to infer from SNP and trait data which SNPs are closest to the gene(s) most strongly affecting trait variation

7.   Development is a result of differential gene regulation in time and space

7.1. Differences among cells result largely from differential gene regulation

7.1.1.   Due mostly to different transcription factors being turned on in different cells

7.2. Hierarchical regulation coordinates gene expression

7.3. "Master regulator" transcription factors are both "required" and "sufficient" for determining a tissue type.

7.3.1.  Skill: know how to design experiments testing "sufficiency" and "requirement" for such transcription factors (i.e. misexpression and knockout mutation experiments)..

7.4. Cancer can result from disruption of regulation (e.g. of cell cycle)

7.4.1.   Know the difference between proto-oncogenes vs. tumor-suppressor genes.

7.4.2.  What would happen if mutations occurred in such genes?

7.5. Development = making a complex multicellular organism from a single cell

7.6. As cell lineages progress from stem cells, cells become more restricted in their potential to become different "fates".

7.7. Cells become different (symmetry is "broken") by asymmetric localization of cytoplasmic determinants and/or induction (extrinsic signaling)

7.8. Three main processes: determination, pattern formation, differentiation (including morphogenesis)

7.9. Hierarchical organization of gene regulation coordinates downstream genes.

7.9.1.  This organization also facilitates coordinated evolution of different aspects of the organism.

8.   Sex is determined genetically in humans (but it's complex) and itself affects the expression of many traits/organs/behaviors/etc. (and it's affected by environment).

8.1. Sex determination occurs at many different levels

8.1.1.  chromosomal, gonadal, somatic

8.2. Many somatic tissues, including brains, show considerable sexual dimorphism that has a genetic basis

8.2.1.  Genetic variation affecting any of these levels can yield ambiguity or mosaicism in different traits associated with sex.

8.2.2.  Skill: What are different ways in which an XY individual could develop into a phenotypic female? How would you test these alternative possibilities?

8.3. Heritable portion of this variation is subject to Selection and thus evolution

8.4. Classical sex/gender "assignment" does not reflect actual biological bases (G+E) for variation in sex/gender phenotypes

8.4.1.  The term "biological sex" is often misused for political purposes. How would a biologist define "biological" sex, and are there only two kinds of outcomes of biological sex determination processes?