Genetics and Heredity Notes
I. Background
A. It was known for 1000s of years that traits were inherited but scientists were unsure about the laws that governed this inheritance.
B. Gregor Mendel (1822-1884) was an Austrian monk who experimented with garden peas and developed the foundation of modern genetics. He noticed that peas had several traits and always showed only one of a pair rather than a blend which was previously believed. He crossed plants with different traits to see what the offspring would look like.
C. Mendel found that no matter what combinations he tried, one trait always dominated and masked the other. It didn’t matter if the trait came from the male or female parent. The traits were controlled by factors which were later known as genes.
D. Mendel’s Laws of Heredity
1. Inherited traits are controlled by genes that occur in pairs. These two versions are called alleles. For example, the gene that controls the color of the flowers in Mendel’s peas has two alleles - purple and white.
2. An organism inherits an allele for each trait from each parent (2 alleles for each trait total)
3. One allele masks the presence of the other. Called the principle of dominance. Dominant (R) vs recessive (r)
4. Alleles separate during meiosis I. Called the law of segregation
E. Vocabulary
1. Homozygous - both alleles for a trait are the same
2. Heterozygous - the alleles for trait are different
3. Genotype - the actual genetic makeup for a trait
4. Phenotype - the way in which the genotype is expressed
II. Monohybrid Cross
A. Mendel found a 3:1 ratio in F2
e.g., round seed wrinkled
P RR x rr
gametes R, R r, r
F1 Rr (all round)
use two F1 individuals as new Parents
P Rr x Rr
gametes R, r R, r
F2 RR, Rr, Rr, rr (round, round, round, wrinkled; 3:1)
B. A Punnett square can be used to show genotype, phenotype, and probability.
e.g., heterozygous purple (Pp) x white (pp)
|
p |
p |
P |
Pp |
Pp |
p |
pp |
pp |
F1 1 purple: 1 white
e.g., two heterozygous tall plants (Tt)
|
T |
t |
T |
TT |
Tt |
t |
Tt |
tt |
F1 3 tall: 1 short
C. Test cross
1. Imagine that you have an organism showing a dominant phenotype. Is the individual homozygous or heterozygous? To be able to say for certain, a test cross is performed.
2. The unknown individual is crossed with a homozygous recessive individual.
3. The genotype of the unknown parent can be deduced from the appearance of the offspring.
III. Dihybrid Cross
A. Mendel wondered if traits always travelled together or if they were inherited separately. e.g., if he crossed a yellow, round plant with a green, wrinkled plant would all the offspring be yellow, round or green, wrinkled or would some be yellow, wrinkled and some green, round
B. He found a 9:3:3:1 ratio in the F2
C. This showed that traits are inherited independently.
e.g., YyRr x YyRrr
|
YR |
Yr |
yR |
yr |
YR |
YYRR |
YYRr |
YyRR |
YyRr |
Yr |
YYRr |
YYrr |
YyRR |
Yyrr |
yR |
YyRR |
YyRr |
yyRR |
yyRr |
yr |
YyRr |
Yyrr |
yyRr |
yyrr |
F1 9 yellow, round: 3 yellow, wrinkled: 3 green, round; 1 green, wrinkled
IV. The probability scale ranges from 0 to 1, where 0 means there is no chance the event will occur and 1 means the event will occur every time. Probability can be calculated using the equation:
P = #correct outcomes
# total outcomes
A. Independent events - the outcome of previous events does not affect the outcome of future events. e.g., the chance of getting heads in a coin toss is ½; the chance of getting heads a second time is ½
B. Rule of Multiplication - The chance of two events occurring together is P1 x P2
C. Rule of Addition - The chance of either one of two possible outcomes occurring is the sum of the two individual probabilities.
V. Cases of Non-Simple Dominance
A. Incomplete Dominance
1. So far, offspring have showed the phenotype of one parent or the other. In some traits, the offspring have a phenotype which seems to be a blend of the two parents.
2. This means that heterozygotes will have a phenotype different from that of the two homozygous genotypes.
3. A 1:2:1 is characteristic of incomplete dominance.
B. Codominance
1. A case in which two alleles are expressed at the same time.
2. The heterozygote phenotype appears to be a blend of the two homozygous phenotypes.
3. An example is roan cattle. A cross between a red bull and a white cow yields roan calves. They calves appear reddish in color but on closer inspection, they have both red and white hairs. In other words, BOTH alleles are expressed..
4. A 1:2:1 is characteristic of codominance.
C. Multiple alleles
1. Many genes actually have more than two alleles.
2. Remember that, although more than two alleles exist in the population, each individual only possesses two - one inherited from each parent.
D. Epistasis
1. A gene at one locus alters the phenotypic expression of a gene at another locus.
E. Polygenic inheritance
1. For some traits, an either-or result for phenotype does not exist. Rather, the phenotype differs along a continuum.
2. Examples are human height and skin color.
VI. Human Genetic Disorders
A. Recessively Inherited
1. Remember that genes code for proteins. An allele that causes a genetic disorder codes for a non-functional protein. Homozygous dominant (AA) and heterozygous (Aa) individuals are normal in phenotype because the one copy of the normal allele produces a sufficient quantity of the protein to prevent the disorder.
2. A homozygous recessive (aa) individual is unable to produce any of the protein in question.
3. Heterozygous individuals are said to be carriers - they have the recessive allele but do not show the recessive phenotype.
4. If the disorder is lethal before reproductive age, no homozygous recessives will reproduce.
5. In general populations, it is unlikely that two carriers of the same disorder will meet and mate. This probability increases, however, in matings between close relatives such as siblings or relatives. In these so called “inbred” matings, there is an increased risk that offspring will have a recessive genetic disorder.
B. Dominantly Inherited Disorders
1. A lethal dominant allele is more rare because even heterozygotes are affected (i.e., die). If the disorder is lethal before reproductive age, the allele will not be passed on. The allele can be perpetuated in the population if it is late-acting.
C. Genetic counselling
1. Carrier recognition
a. Because most children with genetic disorders are born to parents of normal phenotypes, it is important to identify parents who might be carriers before they reproduce.
2. Fetal testing - testing the fetus to determine the presence of any genetic disorders. Fetal testing gives parents the option of
a. Amniocentesis - Beginning around the 14th week of pregnancy, amniotic fluid is withdrawn from the uterus. Some disorders can be detected by the presence of certain chemicals in the fluid while fetal cells present in the fluid can be grown to be used for karyotyping to identify chromosomal abnormalities.
b. CVS - chorionic villus sampling - A small amount of fetal tissue is removed from the placenta and the cells are used for karyotyping. The cells are growing quickly so results are available in 24h as opposed to several weeks as with amniocentesis. CVS can also be performed as early as the 8th wekk of pregnancy.
c. Ultrasound and fetoscopy - these techniques are used to produce and image of the fetus
3. New-born screening - some disorders can be detected at birth by testing the new-born baby.
Chromosomal Theory
VII. Main Points - it was noticed that the behaviour of chromosomes and that of genes were related. (Fig. 14.1)
A. Chromosomes carry genes, the unit of hereditary. Both chromosomes and genes are both present in pairs in diploid cells.
B. Homologous chromosomes separate and alleles segregate independently during meiosis.
C. Fertilization restores chromosomes and genes to pairs.
VIII. Morgan’s Work
A. Morgan was the first to work out that genes are located on chromosomes.
B. He developed a different notation for genetic symbols. For example, the allele for the white eye mutation is symbolized by w, while the normal allele (called the wild type) is symbolized by w+.
C. If the mutation is recessive, a lower case letter is used. Upper case is used for dominant mutant alleles. For example, curly wings is caused by a dominant allele and is symbolized by Cy, while normal wings is Cy+.
D. Sex-linkage (Fig. 14.3)
1. Morgan noticed a male with white eyes among many red-eyed males.
2. He crossed the white-eyed male with a red-eyed female and the F1 were all red, as expected. The F2 was 3 red:1 white. Only males, however, had white eyes and, among males, he noticed there was 1 red:1 white eyes.
3. A karyotype showed that males had a different chromosome from the females - the sex chromosome. Morgan reasoned that the gene for eye color must be located on the sex chromosomes and called the trait sex-linked.
4. Remember that a male always inherits a sex-linked trait from the female parent because the father always supplies the y chromosome.
E. Linked genes and Chromosome Mapping (Fig. 14.4 & 14.5)
1. The number of genes in a cell is far greater than the number of chromosomes so it stands to reason that each chromosome must carry many genes. These genes would tend to be inherited together and are called linked.
2. In some dihybrid crosses, Morgan found that most offspring had the same phenotypes as the parents, but other phenotypes were also observed. How could these other phenotypes arise?
3. Crossing over would occur more often between two genes as the distance between those two genes increased. If this relationship is linear, the frequency of crossing over could be used to determine the distance between two genes on the same chromosome.
4. One “map unit” is defined as 1% crossing over frequency. What is the maximum frequency for crossing over? If two genes are further apart than this value, how can they be mapped?
IX. X-inactivation (Fig. 14.10)
A. In females, one X chromosome in each cell becomes inactivate during embryonic development. The inactivation is random and independent.
B. The chromosome is inactivated by the addition of methyl groups (-CH3) to the DNA.
C. The inactive chromosome condenses and lies near the nuclear membrane. It is called a Barr body.
X. Chromosomal Abnormalities
A. Nondisjunction disorders - result when chromosomes fail to separate normally
1. If two homologous chromosomes move toward the same pole, the daughter cells will be aneuploid. i.e., one will have an extra chromosome while the other will be missing one.
2. After fertilization, a zygote would have either three copies of a chromosome (trisomy) or only one (monosomy), rather than the normal two copies.
3. Each cell of the organism will then have the abnormal chromosome number.
a. Down syndrome
(1) Trisomy of chromosome 21
(2) Symptoms include around, full face; enlarged tongue; short height; large forehead; low mental ability; heart defects; prone to Alzheimer’s and leukemia; mostly sterile.
(3) The frequency is 1 in 2500 for females under 30 years old but increases with the mothers age to about 1 in 100 for females over 30.
4. Nondisjunction of the sex chromosomes
a. Turner’s syndrome
(1) Females have only one X chromosome
(2) Symptoms include failure to develop sexually; usually sterile; short height; thick, wide neck; normal intelligence
(3) Frequency is 1 in 5000
b. Klinefelter syndrome
(1) Individuals have XXy sex chromosomes.
(2) Appear male at birth because of the y chromosome.
(3) Testes fail to develop and sterility results.
(4) The two X chromosomes trigger the development of breasts and other female characteristics.
(5) Frequency is between 1 in 1000 and 1 in 2000 births.
c. XXX females
(1) Trisomic X females are indistinguishable from normal females.
(2) Frequency is 1 in 1000.
d. Patau syndrome
(1) Trisomy 13
(2) Serious eye, brain, and circulatory defects.
(3) Very short life span.
(4) Frequency is 1 in 5000.
e. Edward’s syndrome
(1) Trisomy 18
(2) Affects most body organs
(3) Life span is less than 1 year and is usually less than 10 weeks
(4) Frequency is 1 in 10 000
5. It is possible that nondisjunction occurs in other chromosomes but the consequences are lethal.
B. It is believed that many cases of mental retardation are linked to chromosomal defects.
C. Alteration of Chromosome Structure (Fig. 14.12)
1. Breakage of chromosomes can lead to four changes in structure.
a. Deletion - a piece of a chromosome is lost.
b. Duplication - the piece lost from one chromosome attaches to the homologous chromosome.
c. Inversion - the piece lost from a chromosome reattaches to the same chromosome but in the reverse orientation.
d. Translocation - the piece lost from one chromosome attaches to a nonhomologous chromosome.
2. Deletions and duplications can also occur during crossing over if nonsister chromatids break at different places.
3. Individuals inheriting these chromosomes are missing some genes, resulting in an imbalance which is usually lethal. Inversions and translocations can be problematic as well as many genes function normally only in their proper position in the genome.
D. Genomic Imprinting (Fig. 14.14)
1. Methyl groups are added to nucleotides at specific loci on chromosomes.
2. These methylation patterns differ in males in females. When making gametes, each individual “erases” the imprint from maternal and paternal chromosomes and imprints them with the pattern for his or her own sex
3. Deletion of a section of chromosome 15 causes two different disorders.
a. Prader-Willi - characterized by mental retardation, obesity, short stature, small hands and feet.
b. Angelman - spontaneous, uncontrolled laughter; jerky movements and difficulty with motor control; some mental deficiencies.
c. The disorder that is manifested depends on whether the abnormal chromosome is inherited from the mother (Angelman) or father (Prader-Willi).
4. Fragile X syndrome
a. Is the most common cause of retardation with a genetic basis. It occurs in 1/1500 males and 1/2500 females.
b. The tip of the X chromosome appears severed and hangs from the rest of the chromosome by a thread.
c. Certain sections of DNA normally contain repeats of three nucleotides called triplet repeats. At the tip of the normal X chromosome there are about 50 repeats of the triplet CGG. In fragile X it is repeated 200 times. In “pre-fragile X” the triplet appears between 50 and 200 times but individuals are phenotypically normal. Triplets can be added with each generation until fragile X occurs.
5. Huntington’s disorder - caused by the addition of repeats of the triplet CAG near the tip of chromosome 4.
XI. Extranuclear genes
A. Mitochondria and chloroplasts contain genes of their own
B. These genes are replicated and distributed to daughter organelles independently of normal cell division.
C. Because the sperm donates very little cytoplasm to the zygote, extranuclear genes are inherited from the mother.