From these experiments and several others in Which Mendel studied other traits (e.g., round versus smooth pea pods, smooth versus wrinkled peas, yellow versus green peas, etc.), Mendel was able to put forth two Laws regarding the units of inheritance we now call GENES.

A few important definitions that you should know from now on:

• PHENOTYPE: the physical appearance/expression of a given trait in an organism
• GENOTYPE: the genetic coding of a particular trait in an organism.

• DOMINANT ALLELE: one which masks the expression of another at the same locus
• RECESSIVE ALLELE: one whose expression is masked by another at the same locus.

• a DIPLOID organism (or cell) has two complete sets of chromosomes (one from each parent)
• a HAPLOID organism (or cell) has only ONE set of chromosomes

• HOMOZYGOUS: the two alleles of a gene at a particular locus are the same.
• HETEROZYGOUS: the two alleles of a gene at a particular locus are different.

• A "pure line" or "pure strain" of an experimental organism is one which will always BREED TRUE for a particular trait when self-fertilized or interbred among themselves.
• A TRUE-BREEDING organism, in other words will always produce a known phenotype for a particular trait in question. It is HOMOZYGOUS for that particular trait.

• AUTOSOMAL TRAIT: one which is located on one of the non-sex chromosomes (in species with sex chromosomes)
• SEX-LINKED TRAIT: one which is located on one of the sex chromosomes (in mammals, for example, on either the X (female) or Y (male) chromosome.

SEX CHROMOSOMES

Most species have a defined number of HOMOMORPHIC (same shape) autosomes. In some species, these may influence gender morphology & development.

Usually, however, sex is determined by one (or more) pair(s) of HETEROMORPHIC sex chromosomes.

In mammals, including humans, these are the X and Y chromosomes you've already seen.

NOTE THAT... In species other than Homo sapiens, factors besides a pair of sex c'somes may determine sex, or contribute to sex determination:
• ploidy (e.g. honeybee females are 2n, drones are n)

• alternate alleles (e.g. some fruit flies)

• environmental factors (e.g., incubation temperature of some reptile eggs, such as turtles and even the dinosaurs)

• proportion of X-linked genes (female determining) to autosomal genes (male determining), as in the Mighty Fruit Fly,Drosophila

If sex is determined by heteromorphic sex c'somes, there are four ways it can work:

• XY system: XX - female; XY - male (mammals)

• ZW system: ZW - female; ZZ - male (birds; lepidopterans)

• Xo system: Xo - male; XX - female (lack of male c'some)
  (many insects have this system)

• X & Y c'somes occur in ratios which determine sex.

How does being located on a sex chromosome affect inheritance and expression of a gene?

Let's look at animals with heteromorphic sex chromosomes...(let's consider mammals)

What if a particular allele is located on the X chromosome? In this case, the homolog is the Y, and it has relatively few loci compared to the X.

The X and Y have homologous regions (i.e., with matching gene loci) which pair up during meiosis (synapsis) and undergo limited crossing over. These regions of homology are called PSEUDOAUTOSOMAL regions.

Most of the X and Y are not homologous, however, and undergo no crossing over. Traits located on the DIFFERENTIAL regions of the X and Y exhibit inheritance patterns that are quite different from those shown by autosomal genes, and may be

X-linked (located on the differential region of the X c'some)

Y-linked (located on the differential region of the Y c'some).

Y-linked traits, which exist only in males, are known as HOLANDRIC traits. Females never express them unless a very odd translocation has occured.

Because males have only one allele for all genes located on the X chromosome, they are said to be HEMIZYGOUS for those X-linked traits.

The X chromosome has a relatively large number of functional genes, whereas the Y is believed to have relatively few. A human can survive with a sex chromosome genotype of Xo, but not with Yo, since many vital genes are located on the X.

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Let's do a Punnett Square and consider a trait carried on the X chromosome (and when I say this, you may assume from this point that I'm talking about the differential region of the X, which is most of it) in humans.

• Wild type = regular color vision (trichromatic) - C
• Mutant = red/green color blindness (dichromatic) - c

Because these are carried on the X, DON'T FORGET TO USE THE CHROMOSOMES THEMSELVES IN THE PUNNETT SQUARE. Like so...(those of you who missed lecture will have to figure this out on your own. boo hoo.)

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Also note...

A CROSS is a controlled mating between two specific organisms, usually to obtain progeny of particular genotypes and phenotypes.

A HYBRID is an organism produced by a cross of two parents phenotypically dissimilar, usually for a particular trait of interest.

• A MONOHYBRID cross is one in which only ONE hybrid trait is considered.
• A DIHYBRID cross is one in which TWO hybrid traits are considered.
• TRIHYBRID, TETRAHYBRID, etc. are all crosses in which three, four, etc. number of hybrid traits are monitored in a given cross between two hybrid organisms with two different alleles for each trait in question.

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Mendel named the various generations in any given experimental cross:

• P - Parental generation (the starting pair)
• F1 - First Filial generation = offspring of the P generation
• F2 - Second Filial generation = offspring of two F1 individuals

A BACK CROSS is a mating between a given individual and its parent.

A TEST CROSS is a mating between an individual expressing the dominant phenotype (for a given trait) with an individual who is homozygous recessive for that same trait.

• For example, let's say you have a red-flowering pea plant.
• You know that red is dominant (W) and white is recessive (w) so the genotype could be either WW or Ww.
• To find out what the genotype of the red-flowering plant is, you cross it with a white-flowering plant.
• The resulting phenotypic ratios of the offspring of this test cross should tell you the likely genotype of the red parent.

A RECIPROCAL CROSS is a mating of two phenotypic classes while controlling for the sex of the parent. For example:

• red male pea plant x white female pea plant
• white male pea plant x red female pea plant
  

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Most organisms are diploid. Crosses between diploid parents require a bit of calculation in order to predict phenotypic and genotypic ratios in a given COHORT of offspring.

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Let us learn the wonders of the Punnett Square, a simple matrix. We'll use the handy and adorable GERBIL as our study organism.

In our imaginary study, we're monitoring the inheritance of three traits related to coat color in gerbils:

• hair color: agouti (B) vs. black (b)
• color pattern: solid (P) vs. piebald (p)
• modifier: wild type (M) vs. modified (m) (affects melanin deposition)
  

And so...

• A monohybrid cross for hair color would be: Bb x Bb
• A dihybrid cross hair color and color pattern would be: BbPp x BbPp
• A trihybrid cross for all three traits would be BbPpMm x BbPpMm

  (Note that these are "hybrid" crosses because the parents are hybrids for the traits in question.)

Now we must be sure we understand Mendel's Law of Independent Assortment!

Possible gametes for each trait that either parent can produce:

• Hair color: B or b
• Color pattern: P or p
• Modifier: M or m

Remember that each sperm or egg a gerbil produces will have ONE allele for each of these genes. Let's do a couple of monohybrid crosses to warm up.

(See what happens if you don't come to class? You don't get to do the exercises. Naughty!)

Wasn't that easy? Yes!
It gets complicated only when you start considering more than one trait at at time.

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Let's do a dihybrid cross and consider both hair color *and* color pattern expected in such a cross. The parents we're breeding are hybrid for both traits, and each parent has the genotype:

BbPp

If we are to mate two individuals with this genotype, we represent this cross as:

BbPp x BbPp

Possible gametes either parent should be able to produce:
BP, Bp, bP, bp

[NOTE: We are making the BIG assumption here that the genes we are studying are not located on the same chromosome, which would definitely cloud the picture. We'll return to that in a later lecture.]

Let's do the Punnett Square. From it, you can see that in this typical dihybrid cross, you expect to obtain proportions of

9:3:3:1

meaning...

9 agouti: 3 black: 3 agouti piebald: 1 black piebald babies in the litter.

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You can figure out the expected phenotypic ratios even for a trihybrid cross

(BbPpMm x BbPpMm).

What are the possible gamete types either trihybrid parent could produce?

What are the expected phenotypic ratios? (You fill in the Punnett square)

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Once you start considering more than two or three traits at a time, it becomes incredibly complicated to keep track of what you're doing.

Fortunately, a few simple formulas will help you figure out what to expect from a cross of any number of traits in offspring of a multi-hybrid cross, 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

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We now know that the genetic "factors" (that we now call "genes") are located on the structures inside the nucleus of the eukaryotic cell, the chromosomes.

And you've already had a hint that they can be organized to show their genetic relationships, as shown here.

We'll return to more detailed study of the chromosomes later. For now, just be aware of their existence and very general appearance.

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Pedigree Analysis: Tracing Traits through Family Trees

Modes of inheritance are easy to determine in small, fast-generation organisms. In humans, it's a lot more difficult. We have long gestation periods, relatively few offspring, and we don't like being subjected to controlled matings. For these and other reasons, most early work on the inheritance of human traits was done via PEDIGREE ANALYSIS.

COHORT: all offspring born at a particular time

With data from many generations of humans, one can construct a pedigree chart. This one happens to show the inheritance in one family of a particular rare, recessive allele. Let's trace its appearance throughout the family.

Note that the pedigree chart is a sort of family tree, with specific symbols used as shorthand.

The geneticist works backwards, calculating Mendelian ratios for each group of siblings, and makes a "best guess" about the genotypes of the parents. The more data available, the more accurate the "guess".

In general, one would expect to see the following trends in pedigrees:

AUTOSOMAL DOMINANT TRAIT:

• does not skip generations (unless this is a trait with low penetrance, which we'll discuss for the *next* exam)
• no difference in expression between genders.

AUTOSOMAL RECESSIVE TRAIT:

• tends to skip generations
• no difference in expression between genders
• matings between expressing individuals should produce 100% expressing offspring
• expression incidence increases with consanguinous marriages.

SEX-LINKED DOMINANT TRAIT: (X-linked--not Y-linked)

• tends not to skip generations
• expressing males must have expressing mothers
• expressing female usu. yield 50:50 expressing offspring.
• expressing female must have male OR female parent expressing.
• expressing male will have 100% expressing daughters, and 0% expressing sons.

SEX-LINKED RECESSIVE TRAIT: (X-linked--not Y-linked)

• tends to skip generations
• most affected individuals will be male
• expressing female must have expressing father and either heterozygous or expressing mother.
• expressing female will yield 100% expressing sons.

(the term "affected" can be used interchangeably with "expressing")

Note: Inbred populations tend to express many more recessive alleles than outbred populations.

Outbreeding (breeding between individuals who are not closely related) tends to foster HYBRID VIGOR.

Hybrid vigor is a result of heterozygosity at many loci. This means that few genes are present in homozygous recessive condition--a good thing, since many harmful alleles are recessive!

Inbreeding (breeding between closely related individuals) usually results in homozygosity of recessive alleles at many loci.

The more homozygous recessives you have, the more likely that some of the really bad ones will show up. Can you think of some examples?

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