..Introduction: Quantifying patterns of inheritance.
Mendelian Genetics
Introduction: Quantifying patterns of inheritance.
- People have been breeding economically important species for many generations.
- General Observation: some of the external characteristics of organisms "breed true" while others don't: e.g. gray-coat X gray coat mice typically produces gray-coat offspring.
- The key to understanding these patterns is counting. This was first fully appreciated by a Czech Monk named Gregor Mendel (in about 1866).
Mendel's rules of inheritance, and the patterns revealed by counting
- Mendel studied peas. He focused on flower color (purple or white, flower position (axial or terminal), seed color (yellow or green), seed shape (round or wrinkled).
- He was able to control parentage by emasculating pea flowers, and painting the maternal stigma with pollen, and bagging flowers (techniques plant breeders still use).
- Example:
Purple flowers X White -> all purple offspring. (F1)
"Purple Offspring of P/W cross" X "Purple Offspring of P/W cross" -> 3/4 of offspring are purple, 1/4 (F2), a 3:1 ratio.
What's going on? Some implications (1) the "white factor" isn't lost in breeding with the purple (because white flowered individuals reappear in the F2); (2) there must be--at least--two types of purple flowered individuals (because Mendel knew that both parental types bred true).
Note: a controlled breeding that tracks the inheritance of a single trait is called a monohybrid cross.
- Mendel's explanation:
- Alternative forms of genes must exist, i.e there must be purple flower genes and white flower genes. (We call these alternative forms alleles)
- An individual has two genes for each trait (one from each parent)
- Gametes carry only one allele for each trait.
- If an individual has two different alleles, then only one is fully expressed and the other is masked. We say that the purple color allele is dominant, and white color allele is recessive.
- Some important terminology:
- Locus: the position on a chromosome where alleles for a given trait occur. E. g., we talk about the "flower color locus."
- Homozygote: an individual with a pair of identical alleles at a given locus. So PP and pp individuals are homozygous at the flower color locus.
- Heterozygote: an individual with a pair of different alleles at a given locus. So Pp individuals are heterozygous at the flower color locus.
- Genotype: an individual's actual genetic makeup at a locus. We speak of the Pp and pp genotypes.
- Phenotype: the trait that an individual expresses. So, there are three flower color genotypes PP, Pp and pp, but only two phenotypes purple and white.
- Punnett Square: a technique for visualizing the outcomes of crosses. It's statistics and probability!
- Loci are on chromosomes!
Some complications:
More than one trait.
- Many loci "segregate" independently
- In classical "dihybrid" crosses the F2 Phenotypes occurs in the ratio 9:3:3:1.
Incomplete "dominance" sometimes occurs.
Thought experiment: An RR snapdragon has a red flower, an rr has a white flower, and a heterozygote (Rr) has a pink flower. What ratio of phenotypes do you expect from a pink x pink cross? a pink x red? a pink x white?
There may be more than two alleles at a given locus.
e.g, human blood types.
A gene may have many effects. (Pleiotropy)
There is seldom a single locus-single trait relationship.
Things like skin color, height, etc are controlled by many genes (polygenic) and we often ignore the individual alleles in studying them: we call this quantitative genetics.
Chromosomal mechanics explain Mendel's principles.
- Re-consider what happens in gamete formation (Meiosis) in the F2's of a dihybrid cross.
- But, then genes on the same chromosome
shouldn't segragate independently?
- You're right! Many pairs of genes are on the same chromosome. We say they're linked. Flower color/ pollen grain shape example.
- Crossing over accounts for "sloppy" linkage and has been used to map the positions of genes on chromosomes.
- Genes on the sex-chromosomes (sex-linked traits) have unusual patterns of inheritance.
Summary of basic Mendelian Genetics
- Mendel's Offspring counting and controlled breeding revealed the particulate nature of inheritance. This is consistent with what we know about the mechanics of chromosomes in gamete formation (meiosis).
- There is a critical distinction between Phenotype and genotype. Other important terms: dominant/recessive, homozygous/heterozygous, locus, allele, gene.
- Complications arise when: there is incomplete dominance, more than two alleles at a locus, many genes influence a trait, or when a single gene influenes more than one trait.
- Loci on the same chromosome do not assort independently: they're linked! They provide important information about genetic recombination.
Autosomes and Sex Chromosomes
- Human genetic material is arranged as 22 pairs of "normal" chromosomes we call these autosomes, and 1 pair of sex chromosomes.
- Females have a pair of matching sex
chromosomes called X chromosomes, females are XX. Males have one X
chromsome and one smaller chromosome called a Y, males are XY.
The X and Y chromosome have a small region of homology that allows them to pair during meiotic divisions in spermatogenesis.
- Sex determination: All human eggs have
22 autosomes and 1 X chromosome; human sperm has 22 autosomes and
either an X chromosome, or a Y chromosomes. An egg fertilized by an X
bearing sperm will be a female, an egg fertilized by a Y bearing sperm
will be a male.
Meiotic production of male gametes produces 50% X bearing sperm, and 50% Y bearing sperm.
- Other means of sex determination.
The XY system is one form of heterogametic sex determination. Meaning that different types of gametes determine the gender. In humans and most mammals males produce the different gamete types, but in birds females do (this is the WZ system).
In ants, bees and wasps, and a few other arthropods. Females develop from fertilized eggs and males develop from unfertilized eggs! (That's right male bees have no father!)
In turtles and some lizards sex is determined by the temperature at which the eggs incubate.
Traits on the Sex chromosomes
- Consider the red eye/white eye allele of Drosphilia. R codes for red eyes and r codes for white eyes, with R dominant to r.
- RR and Rr individuals have red eyes and rr individuals have white eyes...In females that is! Because the R/r locus is on the X chromosome.
- This means that males are HAPLOID at the R/r locus; the only genotypes they can have is R or r. An R male has red eyes and r males have white eyes. The recessive phenotype is more common in males. We say the the R/r locus is X-linked.
- A number of important human disorders are X-linked. Hemophila-A in european royal families is a famous example of a X-linked recessive disorder. The most common condition of this type is red/green color-blindness.
Linkage Groups
- Loci on the same chromosome do not assort independently as "simple" Mendelian traits do.
- Assume you inherit alleles A and B on chromosome 12 from your mother, and alleles a and b on chromosome 12 from your father. Your genotype is AaBa, and so we "normally" expect that 1/4th of your gametes would be AB, 1/4th Ab, 1/4th aB and 1/4th ab.
- However, the A and b loci are on the same chromosome, so instead your gametes will be something like 40% AB, 40% ab, 10% Ab and 10% aB. If linkage were perfect there'd be one half AB and one half ab. The gametes of mixed genotype arise because of crossing-over.
- The frequency (or commonness) of
crossing-over can be assessed by performing a "test-cross"
An individual with the dominant A and B alleles on one chromosome and the recessive alternatives a and b on the other is crossed with an individual that is homozygous recessive for both traits.
If linkage were perfect (no crossing over) then such a cross could only produce heterozygotes AaBa. Any "mixed" phenotypes: Aabb (expressing the A phenotype but not the B phenotype) or aaBb (expressing the B phenotype but not the A phenotype) must be products of crossing over.
- The frequency of crossing-over can be used to map genes on the chromosome because loci that are close together are seldom separated by cross-over (they're "tightly" linked).
Other forms of Chromosomal re-arrangement
- Deletion: A portion of a chromosome may be lost. This may be caused by viruses, chemical or radiation.
- Inversions and Translocations:
In inversions the sequence of genes in a region is reversed A-B-C becomes C-B-A.
In translocations a portion of one chromosome becomes incorporated into another, non-homologous, chromosome. e.g. part of chromosome 13 is removed and added to chromosome 17.
- Duplications occur when a sequence of
genes becomes repeated along the the chromosome. For example,
chromsome 9 has the A, B and C loci in sequence, after a duplication
event the same chromosome may have A, B, C, A, B, C.
A syndrome associated with duplications along the X chromosome caused mental redation in affected males.
Duplications may be evolutionarily important.
Changes in Chromosome number
- There to two broad categories:
Aneuploidy a change of plus or minus one in total chromosome (A normal human has 46 chromosomes, an aneuploid human would have 47 or 45 chromosomes).
Polyploidy occurs when an individual has one or more complete sets of chromosomes in addition to the normal diploid number. In humans a normal diploid has 2 x 23=46 chromosomes, so a polyploid would have n x 23 where n is larger than 3, e.g. 3 x 23=69, 4 X 23 =92 (4 x n is called a tetraploid).
A dividing cell is "temporarily" tetraploid after chromosome duplication. So tetraploidy can arise if a cell starts to divide, but doesn't finish dividing.
A 3n polyploid is sterile. Why?
- When a dividing cell fails to divide its
chromosomes equally between its two daughter cells, we call this Non-disjunction
Aneuploidy is cased by non-disjunction.
Down syndrome is the most common form of human aneuploidy. A non-disjunction in egg formation produces an egg with two copies of chromosome 21, when this units with a normal sperm a zygote with three copies of chromosome 21 is produced.
Down's babies exhibit distinctive facial features and reduced mental skills.
- Aberrations of sex chromosome number.
Aneuploidy of the sex chromosomes also occurs, XO, XXY, XXX, zygotes
occur and often survive. Y0 zygotes never survive. Most are sterile
and experience some mental impairment.
XO individuals are sterile, but phenotypically female. XXY individuals exhibit Klinfelter's syndrome--they are slightly "feminized" males. XYY individuals are male are taller than average. Claims that XYY males are more violent than normal, are now disputed.
Information provided by: http://niko.unl.edu