What is a gene? What is the proper way to write human gene names? Do you have two alleles for every gene? Why or why not?

• Gene: a specific sequence of DNA that encodes a particular protein

• Allel: a version of a gene (they exist in the same locus (location) of a chromosome)

  

• Human gene names:

  • ALL CAPS and in italics

  • example: CFTR

What does it mean for a trait to be mono-genic or multifactorial? What is Mendelian inheritance?

• 3 laws of Mendelian inheritance

  • Law of segregation: Offspring inherit one genetic allele form each parent

  • The law of Independent Assortment: the inheritance of one trait is not dependent on the inheritance of another

    • not always the case:

      • monogenic: only one gene influences the observed characteristic

        • eye-color 👁️

      • Multifactorial traits: multiple genes and environmental factors influence observed trait

        • skin color

  • Law of Dominance: An organism with alternate forms of a gene will express the form that is dominant

What does it mean for a trait to be mono-genic or multifactorial? What is Mendelian inheritance?

• monogenic: only one gene influences the observed characteristic

  • eye-color 👁️

• Multifactorial traits: multiple genes and environmental factors influence observed trait

  • skin color

• Mendelian inheritance → always monogenic

Dominant and recessive phenotypes are not the only phenotypes. What are some other examples?

• Incomplete Dominance: the phenotype of a heterozygote is intermediate between the two homozygotes

  • example:

  • 

• Co-dominance: both dominant alleles contribute equally to the phenotype

  • example:

    • eggplant

    • ABO blood group system

      • 

• Epistasis: the expression of one gene modifies the phenotype during the presence of one or more other genes

  • 

Be able to read and interpret which of the five basic inheritance patterns a pedigree is depicting.

• **Pedigrees (**stammbäume): Graphical representation of a family tree with standardized symbols

• Types:

  • Autosomal dominant

  • Autosomal recessive

  • X-linked dominant

  • X-linked recessive

  • Y-linked (patrilineal)

  • Mitochondrial (matrilineal)

• Vocabulary :

  • Proband proposito=male proposita=female family member whom the family is first ascertained: brought to the attention of health care professionals

  • Kindred Extended family covering many generations

  • Sib (sibling) brother or sister

  • Sibship: a series of brothers and sisters

  • 

Be able to calculate the frequency with which autosomal dominant and recessive disorders are inherited given the carrier/affected status of parents. How do offspring of consanguineous fair?

What is consanguinity? How is the coefficient of relationship calculated?

Explain how men are constitutionally hemizygous for most genes on the X-chromosome and women are functionally hemizygous. Why most genes and not all genes? True or False?: Males are never heterozygous for Y-linked sequences. Be able to explain.

• constitutionally hemizygous → if you only have one X chromosome

• functionally hemizygous → in females, due to X-inactivation

• FALSE: because men only have one Y chromosome therefore they are hemizygous

What are examples of patrilineal and matrilineal inheritance? What is heteroplasmy?

• patrilineal inheritance: passing down traus from the father to son

  • example: Y-linked traits ability to produce sperm

• matrilineal inheritance: passing down the trait from mother to offspring( all sexes)

  • example: mitochondrial DNA

• Heteroplasmy: the presence of more than one type of mitochondrial DNA within an individual cells

  • due to mutations in mitochondrial DNA during cells division resulting in a mixture of normal and mutated mitochondria DNA
    

Why is the ascertainment bias high for recessive conditions?

• Ascertainment bias: when a particular trait is overrepresented in a pedigree ( normally recessive disease but more than 1/4 of people have the disease)

• Disease is more common in family than in population

How can two affected parents (of autosomal recessive disease) produce an unaffected child? What is locus heterogeneity? Allelic heterogeneity? Phenotypic heterogeneity? (see also see p. 556 and glossary)

• different locus heterogeneity → the mutations from parents are on a different location on chromosome

  • 

• Allelic heterogeneity refers to the presence of different mutations within the same gene that can cause the same phenotype

  • a different mutations of Cystic fibrosis all cause cystic fibrosis

• Phenotypic heterogeneity refers to the same genotype results in different phenotype

  • example muscular dystrophies

    • 

What is penetrance? Why do we not always see 100% penetrance?

• Penetrance: the likelihood of an individual with a particular genetic mutation developing the condition associated with that mutation

  • example, allergies

  • age-related penetrate due to

    • incremental tissue death

    • loss of function of the normal protein and toxic accumulation of mutant version( pre-diabetic)

    • inability to repair some sort of environmental damage

    • second mutation ( two-hit)

• expressivity: the degree of severity or extent of expression

What is the difference between a mosaic organism and a chimera? How could each occur?

• mosaic organisms: mutation during embryonic development resulting in some cell having the mutations while others do not

• chimera: when a person has at least two distinct genotypes within their body due to a fusion of two embryos during development

What are assumptions made by the Hardy-Weinberg Law?

• The law states that under certain conditions, the frequencies of alleles and genotypes in a population will remain constant from generation to generation.

• Allele frequencies are not changing

  • The population size is infinite

  • Mutations are not occurring

  • Mating is random

  • There is no purifying selection

  • There is no gene flow

Be able to explain how genetic drifts, bottle necks, the founder effect influence allele frequencies.

geneflow: the transferring of genetic diversity among populations resulting in a change on allele frequencies

genetic drift: the random fluctuations of allel frequencies within a population

bottleneck event: an event that causes a severe reduction in population size and the next generation only has the alleles of the small population

founder effect: a type of genetic drift when small group in populations establishes new population and normally less frequent alleles become more common in new population

Why do some genetic mutations remain in the population? Are high mutation rates and unstable genes enough to explain why harmful disease alleles persist? What is balancing selection?

• because mutations are not harmful to current environment or press after giving birth to children

  • tumors

• most disease are in ressiev forms → carries

• must mutations are neutral

• some mutations are advantages to enviriment

  • malaria and sickle cell anemia

• Balancing selection: a type of natural selection which maintains genetic diversity → heterozygous genotype has higher fitness ( due to better adaptation) than homozygous genotypes leading to maintenance of both alles in population

Be able to explain selective sweeps, “hitchhiking alleles” and loss of heterozygosity. (more in 11.4)

• selective sweeps: occur when beneficial mutations arise in a population and rapidly increase due to positive selection. While the mutation spreads it sweeps out or eliminates nearby genetic variation

• hitchhiking alleles: when an allele changes frequency not because it itself is under natural selection but because it is near another gene that is undergoing a selective sweep and that is on the same DNA chain.

• loss of heterozygosity: Heterozygosity refers to the presence of different alleles at a given locus or gene in an individual, and loss of heterozygosity occurs when one allele becomes fixed in the population due to positive selection. This results in a loss of genetic variation at the affected locus or gene.