©2000 Timothy G. Standish Genetic Engineering Timothy G. Standish, Ph. D.
©2000 Timothy G. Standish Jeremiah 23:24 24Can any hide himself in secret places that I shall not...
-
Upload
alvin-sullivan -
Category
Documents
-
view
215 -
download
3
Transcript of ©2000 Timothy G. Standish Jeremiah 23:24 24Can any hide himself in secret places that I shall not...
©2000 Timothy G. Standish
Jeremiah 23:24
24Can any hide himself in secret places that I shall not see him? saith the LORD. Do not I fill heaven and earth? saith the LORD.
©2000 Timothy G. Standish
Beyond MendelBeyond Mendel
Timothy G. Standish, Ph. D.
©2000 Timothy G. Standish
Some traits, when they are tested using Mendel’s techniques, do not produce a 3:1 or 9:3:3:1 ratio Example: When disk shaped and long summer squash are crossed they result in a F2 phenotypic ratio of
9/16 disk, 6/16 sphere and 1/16 long; a 9:6:1 ratio instead of the expected 9:3:3:1 or 3:1 In such cases it is not necessary to abandon Mendel’s basic principle of independent assortment of
genes or the chromosome theory that genes occupy specific loci on chromosomes However, a more subtle understanding is necessary of genes, gene products and alleles
When The Ratios Are WrongWhen The Ratios Are Wrong
©2000 Timothy G. Standish
Exceptions to Mendelian ratios may be accounted for in the following ways:
1 Incomplete or codominance - Two or more alleles exist, but none is dominant to the other/s
2 Multiple alleles for a single gene3 Epistasis - In which interactions between more than one
gene result in a trait4 X-linkage - In which the locus of a gene is on the X
chromosome5 Sex influenced or limited genes, where expression is
influenced or limited by gender or environment
ExplainationsExplainations
©2000 Timothy G. Standish
Incomplete or codominance - Two or more alleles exist, but none are dominant to the other
Incomplete dominance results in blending of the parental traits
Example: In four O’clock flowers (and others) red crossed with white results in pink F1 progeny
1 Incomplete Or Codominance1 Incomplete Or Codominance
XX
©2000 Timothy G. Standish
F2 results show this is not blended inheritance
1 Incomplete Or Codominance1 Incomplete Or Codominance
F1P
XX
CRCWCRCR CWCW
CRCR
CRCW
CRCW
CWCW
CR CW
CR
CW
F2 GenerationF2 Generation
2: 11:
In the F2 generation a 1:2:1 ratio results of red to pink to white
©2000 Timothy G. Standish
ErythrocyteErythrocyte
Membrane
Cytoplasm
Codominant traits show up clearly whether the other allele is present or not
Example: MN blood group genes in humans are codominant
1 Incomplete Or Codominance1 Incomplete Or Codominance
M
M
M
M antigen
Anti M antibodies
M phenotypeMM genotype
©2000 Timothy G. Standish
ErythrocyteErythrocyte
Membrane
Cytoplasm
Codominant traits show up clearly whether the other allele is present or not
Example: MN blood group genes in humans are codominant
1 Incomplete Or Codominance1 Incomplete Or Codominance
N antigen
Anti N antibodies
N phenotypeNN genotype
N
N
N
©2000 Timothy G. Standish
ErythrocyteErythrocyte
Membrane
Cytoplasm
Codominant traits show up clearly whether the other allele is present or not
Example: MN blood group genes in humans are codominant
1 Incomplete Or Codominance1 Incomplete Or Codominance
M
M
M and N antigens
Anti M antibodies
MN phenotypeMN genotype
NAnti N antibody
©2000 Timothy G. Standish
2 Multiple Alleles2 Multiple Alleles Any gene with two or more alleles is said to have
multiple alleles Mendel worked with only two allele systems, but
variations from the kind of results he obtained occur when more than two alleles are involved
Note that while individuals cannot have more than two alleles for a given gene, populations can have many different alleles
Human ABO blood types provide an excellent example of multiple alleles in human populations
©2000 Timothy G. Standish
2 Multiple Alleles2 Multiple Alleles ABO blood types are determined by the presence of antigens
on the surface of erythrocytes in much the same way as MN blood types
The antigens are oligoscaccharides presented on the cell surface
Almost everyone makes an oligosaccharide called “H substance” which is a chain of sugars joined together in the following order:
L-fructose ˜ b galactose ˜ N-acetylglucosamine Individuals with O type blood only display the H substance on
their erythrocytes
©2000 Timothy G. Standish
2 Multiple Alleles2 Multiple AllelesType A and B blood result from the presence
of enzymes which add a sugar to the H substance
Type A individuals produce an enzyme that adds N-acetylgalactosamine to the galactose in the H substance
Type B individuals express a very similar enzyme that adds galactose to the same place
©2000 Timothy G. Standish
2 Multiple Alleles2 Multiple Alleles If neither enzyme is expressed type O blood results If the N-acetylgalactosamine adding enzyme is
present type A blood results If the galactose adding enzyme is present type B
blood is made If both the N-acetylgalactosamine and galactose
adding enzymes are present, type AB blood results As the enzymes are coded for by genes, blood type is
under direct genetic control
©2000 Timothy G. Standish
When a single trait is controlled by more than one gene epistasis may result
The squash example we started with is an example of epistasis
Understanding biochemical pathways helps us understand epistasis
EpistasisEpistasis
B CA 21 DC
A3
1
D2
B
©2000 Timothy G. Standish
EpistasisEpistasis
B CA 21
If the gene for enzyme 1 was knocked out, the flower would be colorless
B CA 21
X
Imagine that this pathway produces a red pigment, C, in flowers and that A is a colorless precursor and B is a yellow intermediate
©2000 Timothy G. Standish
EpistasisEpistasis
B CA 21
If the gene for enzyme 1 was knocked out, the flower would be colorless
B CA 21
X
Imagine that this pathway produces a red pigment, C, in flowers and that A is a colorless precursor and B is a yellow intermediate
If the gene for enzyme 2 was knocked out, the flowers would be yellow
©2000 Timothy G. Standish
EpistasisEpistasis
B CA 21
Because enzymes can catalyze many reactions in a short period of time, the presence of just one copy of a gene is typically enough to mask the absence of a bad copy
Thus an individual heterozygous for enzyme 1 could still produce intermediate product B
B CA 21X X
If both genes were knocked out, the flowers would be colorless
©2000 Timothy G. Standish
Consider a cross between a two individuals heterozygous for both enzyme coding genes
Lets call the functional enzyme 1 gene 1F and the mutated gene producing nonfunctional enzyme 1, 1n
We will use the same convention for enzyme 2 with genes 2F and 2n
Our cross would look like this:
EpistasisEpistasis
1F1n2F2n X 1F1n2F2n
©2000 Timothy G. Standish
11FF11nn22FF22nn XX 11FF11nn22FF22nn
1F2n
1n2F
1n2n
1F2F
1n2n1n2F1F2n1F2F
1F1n2F2n1F1n2F2F1F1F2F2n
1F1n2n2n1F1n2F2n1F1F2n2n1F1F2F2n
1n1n2F2n1n1n2F2F1F1n2F2n1F1n2F2F
1n1n2n2n1n1n2F2n1F1n2n2n1F1n2F2n
1F1F2F2F
©2000 Timothy G. Standish
11FF11nn22FF22nn XX 11FF11nn22FF22nn
1F2n
1n2F
1n2n
1F2F
1n2n1n2F1F2n1F2F
1F1n2F2n1F1n2F2F1F1F2F2n
1F1n2n2n1F1n2F2n1F1F2n2n1F1F2F2n
1n1n2F2n1n1n2F2F1F1n2F2n1F1n2F2F
1n1n2n2n1n1n2F2n1F1n2n2n1F1n2F2n
1F1F2F2F
©2000 Timothy G. Standish
– 10:3:3 = (9+1):3:3– 10:6 = (9+1):(3+3)– 13:3 = (9+1+3):3
A 9:4:3 RatioA 9:4:3 Ratio
– 9:7 = 9:(3+3+1)– 12:3:1 = (9+3):3:1– 12:4 =(9+3):(3+1)
A ratio made up of some combination of 9:3:3:1 is generally a good hint that epistasis is at work
A biochemical pathway like the one discussed will result in a 9:4:3 ratio as long as there are two alleles each of which behaves in a simple dominant/recessive way
The 9:4:3 ratio is really a 9:(3+1):3 ratio Other possible phenotypic ratios for a
dihybrid cross involving epistasis include:
©2000 Timothy G. Standish
Agouti Mice - A 9:4:3 RatioAgouti Mice - A 9:4:3 Ratio
Mice lacking yellow or black are albino
Brown mice actually exhibit agouti coloration, a mix of yellow and black with hair strands alternating yellow and black melanin pigment
Yellow Black AlbinoAgouti
Mutating a gene coding for an enzyme necessary to make black pigment results in yellow mice
Mutating an enzyme for yellow results in black
©2000 Timothy G. Standish
Agouti Mice - A 9:4:3 RatioAgouti Mice - A 9:4:3 Ratio
ColorlessPrecursor
YellowY
AgoutiB
Black
ColorlessPrecursor
Yb
yB
yb
YB
ybyBYbYB
YyBbYyBBYYBb
YybbYyBbYYbbYYBb
yyBbyyBBYyBbYyBB
yybbyyBbYybbYyBb
YYBB
ColorlessPrecursor
Y Agouti/Yellow
BBlack
Two possible explanations of agouti
Two possible explanations of agouti
Cross two agouti individuals who
are both heterozygous
YyBb X YyBb
©2000 Timothy G. Standish
Agouti Mice - A 9:4:3 RatioAgouti Mice - A 9:4:3 Ratio
ColorlessPrecursor
YellowY
AgoutiB
Black
ColorlessPrecursor
Yb
yB
yb
YB
ybyBYbYB
YyBbYyBBYYBb
YybbYyBbYYbbYYBb
yyBbyyBBYyBbYyBB
yybbyyBbYybbYyBb
YYBB
BlackAgouti/Yellow
ColorlessPrecursor
YB
Two possible explanations of agouti
Two possible explanations of agouti
Cross two agouti individuals who
are both heterozygous
YyBb X YyBb
©2000 Timothy G. Standish
As mentioned earlier, the F2 generation of a cross between a disk shaped and a long squash has a disk:spherical:long ratio of 9:6:1
How can this ratio be explained? In the F2 generation the following genotypes
must result in the indicated phenotypes
Another Example Of Epistasis:Another Example Of Epistasis:Fruit Shape In Squash, A 9:6:1 RatioFruit Shape In Squash, A 9:6:1 Ratio
9 A_B_3 A_bb3 aaB_1 aabb Long
Disk
Sphere
©2000 Timothy G. Standish
4 X-Linkage4 X-Linkage Thomas Hunt Morgan was the first to associate a trait
(gene) with a chromosome. Worked with fruit flies (Drosophila melanogaster) In humans and Drosophila, males are XY Thus males are haploid for the X chromosome Because of this, recessive genes on the X chromosome
show up far more commonly in male than female phenotypes
©2000 Timothy G. Standish
DrosophilaDrosophila Nomenclature Nomenclature
+ = Wild type, phenotype in nature (i.e. red eyes and round wings)
Mutants are alternatives to the wild type Fruit fly genes are named after the mutant Dominant mutations are capitalized (i.e. Hairless or
H and Bar or B) Recessive mutants are named using lower case
letters (i.e. black or b and white or w)
©2000 Timothy G. Standish
Sex DeterminationSex Determination Two ways in which sex can be determined: Environment:
Turtles - Temperature of development Some fish - Social structure
Chromosomes - Three methods: XO - Haploid/diploid ie bees, haploid males diploid females ZW - Heterogametic (ZW) females, homogametic (ZZ) males, ie
birds XY - Heterogametic (XY) males, homogametic (XX) females, ie
humans and Drosophila
©2000 Timothy G. Standish
Morgan’s Discovery Of An X-Morgan’s Discovery Of An X-Linked Linked DrosophilaDrosophila Gene Gene
A white-eyed male was discovered
X+ X+
X+Y
Xw X+
XwY
X+ Xw
X+
Y
Xw X+
X+Y
Xw X+
X+Y
X+ X+
Xw
Y
X P
X F1
F2
1/21/4 1/4
©2000 Timothy G. Standish
The Key To Morgan’s DiscoveryThe Key To Morgan’s Discovery The key to Morgan’s discovery was the observation that all
the white eyed individuals in the F2 generation were males
Without this vital data on the association of white eyes with being male, the gene for white eyes could have been seen as a simple recessive trait on an autosome
This illustrates the importance of recording all the data possible and being alert to the possibility of interesting things being present in the data
“Fate favors the prepared mind” (Louis Pasture)
©2000 Timothy G. Standish
Human X-linked Recessive Human X-linked Recessive GenesGenes
Brown enamel - Tooth enamel appears brown rather than white
Hemophilia - Two types:– A - Classic hemophilia, deficiency of blood
clotting factor VIII
– B - Christmas disease, deficiency of blood clotting factor IX
©2000 Timothy G. Standish
X-linked Recessive GenesX-linked Recessive GenesRelated to sightRelated to sight
Coloboma iridis - A fissure in the eye’s iris Color Blindness - Two types:
– Deutan - Decreased sensitivity to green light– Protan - Decreased sensitivity to red light
Congenital night blindness - Not due to a deficency of vitimin A
Mocrophthalmia - Eyes fail to develop Optic atrophy - Degeneration of the optic nerves
©2000 Timothy G. Standish
Royal PedigreeRoyal Pedigree
Albert of Saxe-Coburg (18XX-18XX)
Edward Duke of Kent (1767-1820) Victoria Princess of Saxe-Coburg (1786-1861)
Emperor Frederick III of Germany (1831-1888)
Victoria (1840-1901)
Victoria Queen of England (1819-1910)
Leopold Duke of Albany(1853-1884)
Victoria(1866-1953)
King Alfonso XIII of Spain (1841-1910)
Beatrice(1857-1944)
Alice(1843-1878)
Tsar Nicholas IIof Russia (1868-1918)
Irene(1866-1953)
King Edward VII of England (1841-1910)
Alix (Alexandra)(1872-1918)
Olga(1895-1918)
Alexis(1904-1918)
Anastasia(1901-1918)
Marie(1899-1918)
Tatiana(1897-1918)
©2000 Timothy G. Standish
Expression of genes that are not necessarily on the X chromosome may be influenced by the gender of the individual
One major reason for this is the impact that steroid sex hormones have on the expression of genes
Male pattern baldness is the classic example of a sex influenced gene in humans
5 Sex-Influenced Or Limited Genes5 Sex-Influenced Or Limited Genes
Genotype Phenotype
Female Male
BB Bald Bald
Bb Flocculent Bald
bb Flocculent Flocculent
©2000 Timothy G. Standish
Genes do not work in isolation, but their expression is influenced by their environment
Just as expression of sex influenced genes are influenced by the hormones in their environment other environmental variables impact expresson of most genes
Environmental EffectsEnvironmental Effects
Being Himalayan gives a whole new meaning to the term “brown nosing.”