4. Describe nondisjunction and cross-over.
4. Distinguish between phenotype and genotype, dominant and recessive, homozygous, and heterozygous
5. Be able to use Punnett squares to solve simple genetics problems
6. Distinguish between incomplete dominance, polygenic inheritance, and multiple alleles.
7. Solve X-linked genetics problems
8. Distinguish between sex-linked and sex - influenced traits
9. Use pedigree charts to determine if a disorder is dominant, recessive, or X-linked; determine the genotype f individuals in these charts.
Genetics
Whole organisms are the results of the expression of many genes
Variable characteristics of an organism are called phenotypes
each of which is controlled by one or more genes.
Simple viruses have only a few genes
Complex organisms like us have ~125,000 (exact number not yet known)
Genes were discovered first by Mendel in 1860’s
Genes have a physical reality. They can be localized and studied at the molecular level.
Chromosomes
Late 1800’s people began to realize that behavior of genes and alleles particularly regarding gamete formation was analogous to the behavior of chromosomes during meiosis
Genes lie on chromosomes
Each cell in a human has many chromosomes each containing 100’s - 1000’s of genes
Alleles come in pairs - so do chromosomes
Each member of a pair has the same genes but may have different alleles
a A
B B
c c
D d
E E
f F
In this case each chromosome has 6 genes, 3 of which are identical
Humans have 23 pairs of chromosomes, 22 of which work like above example
Mitosis and Meiosis
Mitosis assures that all cells in the body are diploid and have same number and kind of chromosomes
Prophase, metaphase, anaphase, and telophase
The cell cycle includes interphase, where cell growth and DNA replication occurs.
Meiosis requires two cell divisions
During the first cell division homologous chromosome pairs (one pair from each parent) separate
During the second division sister chromatids separate.
The resulting cells or gametes are haploid
Karyotypes
Except for the 23rd or sex chromosome, each chromatid of a chromosome pair carries more or less the same genes
Total number of genes ~125,000
125,000/23 = ~5000 unique genes
Human chromosomes vary widely in size, each contain 1,000 - 10,000 genes each
The chromosomes visible in a metaphase cell make up the cell’s Karyotype.
Chromosomes are grouped and numbered according to size and other features.
So far at least 2300 genes have been mapped onto chromosomes (includes 611 disease related ones)
Crossover
During meiosis I, homologous chromosomes are in close proximity.
Non-sister chromatids can exchange genetic material
This and two other factors ensure genetic diversity in offspring
Crossing-over can recombine genes in homologous pairs
Following meiosis each gamete has a different combination of chromosomes
Upon fertilization, recombination of chromosomes occurs.
Process of nondisjunction can produce abnormal karyotypes
Caused by a failure of homologous chromosomes to separate in meiosis I
Or sister chromatids to separate during meiosis II
In either case the result is some gametes with twice as many of a particular chromosome and others with none
Down’s syndrome results from an extra copy of chromosome 21
Turner syndrome female with XO
Klinefelter syndrome males with XXY
Metafemales XXX (relatively benign)
XYY males
Damaged chromosomes can also result in abnormal karyotypes
Fragile X-syndrome
Crie du chat (part of one chromosome 5 missing)
Mendellian Genetics
Mendel studied the inheritance of traits in peas but his results apply to all organisms
Example of Mendelian Genetics:
Two traits in corn:
Seed Color Kernel Shape
red yellow wrinkled smooth
Each kernel (seed) is an individual offspring
Rules of Mendellian Genetics
Results of this type of experiment led Mendel to the following conclusions:
Traits are determined by genes. In simplest form , one gene --> one trait.
Each gene comes in different forms ("alleles") which correspond to different forms of each trait (e.g. attached vs. unattached earlobes)
In many cases, presence of one allele masks the effect of (is "dominant" over) the other allele(s) which is called recessive
In higher organisms, at least, there are two copies of each gene in each cell ("diploid" state); the two copies need not be identical alleles
When gametes (egg & sperm) are formed, each get only one member of each pair of alleles ("haploid")
When gametes form, the alleles for one trait are distributed independently of those for other traits
For 2 traits each with 2 alleles:
4 types of gametes in equal proportions
(sometimes only approximately true)
When gametes fuse to a zygote, two copies each gene will be restored, one from each parent
Distribution of alleles when gametes form and fuse determined by simple rules of probability
Examples of ìcrossesî from corn
A. Monohybrid cross
red and yellow seed color
P1 x P1 red x yellow
F1 all red
F1 x F1 110 red, 40 yellow (ratio 2.75 red, 1 yellow)
B. Dihybrid cross
P1 x P1 red, smooth x yellow, wrinkled
F1 all red, smooth
F1 x F1 124 red, smooth; 35 red, wrinkled;
42 yellow, smooth; 8 yellow, wrinkled
ratio 9:2.54:3.05:0.6
Analyzing crosses with ìPunnett Squaresî
A: Monohybrid cross
R = red
r = yellow
P1 x P1
|
phenotype = "yellow", genotype r/r 1.0 r |
|
|
phen. "red" |
|
|
1.0R |
1.0 R/r |
|
gen. R/R |
All offspring red since 100% occurrence of R/r. Red is dominant over "yellow"
R/R and r/r are homozygotes
R/r is a heterozygote
F1 x F1
|
Phenotype = red, genotype R/r |
|
|
0.5R 0.5r |
|
|
phen 0.5R |
0.25 R/R 0.25 R/r |
|
= "red’ |
|
|
0.5 r |
0.25 R/r 0.25 rr |
|
gen = R/r |
Since only rr is yellow ratio red to yellow expected 3:1
Since rr reappears in the F1 x F1, r alleles are real, discrete entities and are not lost in F1 by "blending"
B: Dihybrid Cross
R = red r = yellow Su = smooth su=wrinkled
P1 (R/R Su/Sux) x P1 (r/r su/su)
|
1.0 rsu (possible gametes) |
|
|
1.0 RSu |
1.0 R/r |
|
(possible gametes) |
phenotype off P1 x P1 is red, smooth since red (R) dominant over yellow (r), smooth (Su) dominant over wrinkled (su).
F1 (R/r Su/su) x F1 (R/r Su/su)
|
0.25 RSu |
0.25 rSu |
0.25 Rsu |
0.25 rsu |
|
|
0.25 RSu |
0.0625 RRSuSu |
0.0625 RrSuSu |
0.0625 RRSusu |
0.0625 RrSusu |
|
0.25 rSu |
0.0625 RrSuSu |
0.0625 rrSuSu |
0.0625 RrSusu |
0.0625 rrSusu |
|
0.25 Rsu |
0.0625 RRSusu |
0.0625 rRSusu |
0.0625 RRsusu |
0.0625 Rrsusu |
|
0.25 rsu |
0.0625 RrSusu |
0.0625 rrSusu |
0.0625 Rrsusu |
0.0625 rrsusu |
X& Y chromosome
Genes on the 23rd or Sex chromosome pair works differently from those on autosomal chromosomes
An X chromosome has many genes, a Y chromosome just a few.
Most of the genes on the Y chromosome do not have counterparts on the X
Humans with 2 X chromosomes are female
Humans with 1 X and 1 Y are male
Females have two copies of X chromosome genes
Humans have 46 chromosomes/ cell
Traits due to genes on X-chromosome called X-linked
Will be inherited differently males and females.
Sex-linked traits
In principle can have X-linked (only on X)
and Y-linked (only on Y) genes
X-linked most common
Color blindness , hemophilia, Duchenne muscular dystrophy X-linked
Sex Influenced traits:
Characteristics that appear in one sex but seldom in the other
Probably due to genes that are turned on or off by hormones
Male -pattern baldness caused by testosterone
Gene is dominant in males but recessive in females
More definitions:
Incomplete dominance:
Sometimes a "genotype" has a phenotype 1/2 way in between AA and aa genotypes
Codominance:
Two different alleles and effects of both can be seen in phenotype
Polygenic traits:
Many traits in humans due to effects of more than one gene
Limited Penetrance:
A certain allele/genotype produces characteristic phenotype only under certain environmental conditions
Examples of Human Genetics with Medical Implications
Probably all cancers are caused by changes in genes
Sometimes dominant genes are responsible
Sometimes it is recessive i.e. individual must have two copies of culprit gene to get cancer
Genes responsible for DNA repair can have these malfunctions
Recessive Disorders
Take two alleles
Heterozygote parents called "carriers"
Asymptomatic
Cystic Fibrosis, Tay - Sachs Disease,
Phenylketonuria (PKU)
Codominance
Human blood groups (A, B, O)
"Tissue types" i.e. histocompatability antigens
Polygenic traits
size, skin color, intelligence (to some extent)
Disorders include clubfoot, cleft palate, neural tube defect
Autosomal dominant disorders
Only one allele needed
Neurofibromatosis, Huntington disease.
Incomplete dominance
Sickle -cell disease
HbsHbs have sickle-cell disease
HbAHbA are normal
HbAHbS have sickle cell trait
offers protection against malaria