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    Why Do Related Individuals Resemble Each Other?

    Humans have been trying to understand this for a long time.
    Our modern understanding had precursors, including

    • "Blending" inheritance (Aristotle, Nageli, Darwin)
        Offspring traits were a 50/50 mixture of the traits of each parent.

    • Inheritance of Acquired Traits (Lamarck)
        Traits acquired during an individual's lifetime could be passed on to their offspring. Use or disuse of a structure would cause the structure to become more or less developed, respectively.

    But does it really work that way?

Classical Mendelian Genetics: Single Gene Inheritance

    The study of intergenerational inheritance patterns
    is also known as transmission genetics.

    Gregor Mendel published Versuche uber Pflanzenhybriden
    (Experiments on Plant Hybridization) in 1866.

    Although its importance was not recognized at its publication,
    Mendel's work eventually changed the course of biology.


    Quantitative Traits

    The earliest studies of inheritance focused on quantitative traits.

    A quantitative (= continuous) trait

    • is a phenotype resulting from the cumulative actions of more than one gene.
    • is thus said to be polygenic.
    • can vary among individuals to produce a continuous distribution of phenotypes.

      examples:

      • stature/height
      • eye color
      • hair/fur color
      • cranium size
      • body scent
      • color pattern of shells
      • flower shapes and colors
      • actually....most traits

    Add the effect of environmental influence on the traits,
    and you get something very difficult to characterize.

    Because of the complex inheritance pattern of quantitative traits,
    there was little true understanding of inheritance.

    And then along came Gregor Mendel.

    Qualitative Traits

    Mendel was the first to investigate qualitative traits.

    A qualitative (= discrete) trait

    • is a phenotype resulting from the action of a single gene.
    • is thus said to be monogenic.
    • expressed as a discrete phenotype.

      examples:

      • human ABO blood types
      • human ear wax - wet vs. dry
      • human cystic fibrosis
      • human Huntington's disease
      • human Sickle Cell Anemia
      • dwarfism in many mammals
      • many traits in sweet peas
      • actually....most traits

    Because of their relatively simple "either/or" inheritance patterns,
    qualitative traits could more easily be characterized than quantitative traits.

    As Mendel discovered, it's a simple matter of statistics.

Mendel's Laws of Genetics

The simple inheritance patterns of qualitative traits allowed Mendel to devise two Laws of Genetics:

Law of Segregation (Mendel's First Law)

    Every (diploid) individual carries two copies of every gene,
    one from each parent.

    When that individual produces gametes, the two gene copies
    separate from each other and migrate to separate daughter cells.

    Each gamete contains only one copy of the gene.

Law of Independent Assortment (Mendel's Second Law)

    When an individual produces gametes,
    the various genes inherited from each parent (i.e., in each set)
    migrate into new daugher cells independently of one another.

    Multiple Alleles --> Phenotypic Variation

    A monogenic trait varies only when there is more than one allele in the population.

    With respect to a monogenic trait...

    • wild type - the phenotype most common in a natural population
    • mutant - any phenotype other than wild type

    Mutants for study can be obtained via

    • screening - examining many individuals to find mutant variants

    • induction - subjecting model organisms to mutagens
      (e.g., chemicals, ionizing radiation) to induce
      heritable mutations in the germline.

    Punnett Square: A Null Hypothesis

    The probability of any given genotype being inherited by an offspring
    from its parents can be calculated with a Punnett Square.

    Since the alleles of a gene separate from each other during gamete formation,
    each allele can be placed by itself on a matrix.

    Complete the matrix to see the possible allele combinations and their probability.

    This can be done for any number and combination of monogenic traits.
    But it gets a bit unwieldy with more than two or three.


    The top illustration shows a monohybrid cross.
    Each parent is heterozygous (hybrid) for one trait.

    genotype probabilities:
    • BB = 25%
    • Bb = 50%
    • bb = 25%
    • that is, 1:2:1
    phenotype probabilities:
    • pink (dominant) = 75%
    • white (recessive) = 25%
    • that is, 3:1


    The bottom illustration shows a dihybrid cross.
    Each parent is heterozygous (hybrid) for two traits.

    genotype probabilities:
    • 1/16 (6.25%) of any combination
    phenotype probabilities:
    • both traits dominant = 9/16
    • pea color dominant/pod color recessive = 3/16
    • pod color dominant/pea color recessive = 3/16
    • both traits recessive = 1/16
    • that is, 9:3:3:3:1

Meiosis: The Chromosomal Basis of Mendel's Laws

Understanding how chromosomes migrate during mitosis and meiosis allows us to better understand Mendel's Laws.

A diploid organism inherits only one allele of every gene from each parent.

When that individual produces gametes, the genes and alleles it inherited from its parents will migrate in specific ways.

    Meiosis: Segregation

    Mendel did not know about chromosomes or meiosis.

    But we now know that the migration of chromosomes
    carrying their various genes (and alleles thereof)
    is the explanation for Mendel's Law of Segregation.

    Meiosis: Independent Assortment

    When an individual undergoes meiosis, its
    maternal and paternal chromosomes segregate at meoisis I.

    They do so independently of one another.

    This means that the alleles of maternal and paternal chromosomes
    can end up in different, random combinations.

Transmission Genetics Terminology

Mendelian genetics is also known as transmission genetics.
Understanding its terminology is the first step to understanding its mechanisms.

autosome

a trait encoded by gene(s) on one or more autosomes
sex chromosome

a chromosome involved in determining the sex of an organism.
examples: X and Y chromosome of mammals; Z and W chromosomes of birds.
sex-linked trait

a trait encoded by gene(s) on a sex chromosome
example:
  • a gene located on the X chromosome is X-linked
  • a gene located on the Y chromosome is Y-linked
cross

a controlled mating between two organisms, usually to obtain progeny
of particular genotypes and phenotypes;
typically represented as shorthand such as PP x Pp
true-breeding

an organism homozygous for a particular trait;
A true-breeding will always "breed true" (produce offspring of its phenotype)
when bred to another organism true-breeding at the same gene locus.
hybrid

an organism that is heterozygous for a particular trait;
an organism produced by a cross of genotypically different parents.
monohybrid cross

a mating of two hybrids in which in which only ONE heterozygous locus is considered;
example: Aa x Aa
dihybrid cross

a mating of two hybrids in which in which two heterozygous loci are considered;
example: AaBb x AaBb
multihybrid cross
(trihybrid, tetrahybrid, etc.)

a mating of two hybrids in which in multiple heterozygous loci are considered;
example: AaBbCc x AaBbCc
parental (P) generation

the starting pair of individuals in a series of crosses
first filial (F1) generation

offspring of the P generation
second filial (F2) generation

offspring produced by the mating of two F1 individuals
back cross

a mating between a given individual and one of its parents
(or another individual of the parental genotype)
test cross

a mating between an individual expressing the dominant phenotype of a given trait
with an individual that is homozygous recessive at the same locus
reciprocal cross

a mating of two phenotypic classes in which the parental sex is controlled

Test Cross: A Closer Look

    A test cross is a mating between an individual expressing the dominant allele of a particular gene and an indivdual homozygous recessive at that same locus.

    Offspring phenotypic ratios can reveal whether the dominant expressing parent is homozygous or heterozygous.

x

Reciprocal Cross: A Closer Look

    A reciprocal cross is a mating of two phenotypic classes
    while controlling for the sex of the parent.

    The results can reveal whether the sex of the parent
    has any influence on the inheritance of the trait in question.

    x


    The example on the right shows reciprocal crosses
    between true-breeding parental fruitflies.

  • FIRST CROSS
    • P red-eyed female x white-eyed male
    • F1 progeny are 100% red-eyed (males and females)
  • RECIPROCAL CROSS
    • P white-eyed female x red-eyed male
    • F1 progeny are 50% red-eyed females
    • F1 progeny are 50% white-eyed males

    This reveals that the trait in question is X-linked recessive.


Practice with a Model System: The Agouti Gene

The agouti locus is involved in many important metabolic functions.
Hair color is only one of its phenotypic manifestations.

Many different mammals express the wild type agouti hair pattern:


    Model Organism: The Mongolian Gerbil (Meriones unguiculatus)

    The Parental Generation: True-breeding individuals.

    Agouti (A) is dominant to black (a).

    • Augie is a homozygous wild type agouti male (AA)
    • Mable is a homozygous mutant melanistic female (aa)

F1 x F1 Cross

Mate two of the F1 siblings together.

Dihybrid Cross

Genes on different chromosomes assort independently of one another.

Thus, any trait not on the same chromosome as the agouti locus should assort independently of the agouti locus.

Piebalding, the presence of white patches on the skin and fur,
is controlled by the S locus.
The A and S loci are located on different chromosomes.

Solid color (S) is dominant to piebald (s).

Dihybrid Punnett Square Solution

Multi-hybrid Crosses

A Punnett Square rapidly becomes unwieldy as more loci are added.
Fortunately, a few simple formulas allow quick predictions of genotypic and phenotypic ratios.
If n equals the number of traits/genes in question...

 

Number of F1 gamete types

2n

Proportion of F2 homozygous recessives

1/(2n)2

Number of different F2 phenotypes
(complete dominance)

2n

Number of different F2 genotypes
(or phenotypes, if no dominance)

3n



Dihybrid Punnett Square Solution: