Ch. 5 – Inheritance Patterns, Phenotype Variability, and Allele Frequencies.

%%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.%%

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• 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

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%%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 \n

%%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

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%%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.

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