Download AG2010 lecture 1_basic genetics

ADVANCED GENETICS
Genetic Principle
January 25, 2010
For the pleasant spring…
Things to keep in mind before it’s too late
• Homework accounts for half of the total grade
and help you study for prelim (genetics prelim).
• Often times drawings with concise explanations
are really welcomed.
• Grant/grant/grant…start early.
• Homework due dates will be noticed on website.
• Question sessions before and after homework
due every Thursday after class: covered contents
are by request.
1
The Basics
Specific segment of DNA in a discrete region of a
chromosome that encodes a particular RNA or protein is
gene
_________.
alleles
Genes exist in alternative forms called _________.
2 alleles for each gene.
Each diploid individual inherits _____
When the two alleles are the same, the individual ishomozygote
_____
When the two alleles are different, the individual isheterozygote
_____
Alleles interact with one another. For instance, when the
phenotype of allele 1 masks the phenotype of allele 2, allele
dominant with respect to allele 2. Allele 2 is
1 is _________
recessive with respect to allele 1.
_________
The Punnet square:
Visual summary of a cross
3:1
2
Mendel’s genetics - the classic
General observations
• The phenotype expressed in F1
generation is determined by dominant
allele.
• Recessive allele phenotype reappears
in the F2 generation.
Mendel’s genetics - the classic
Law of Segregation
Two alleles of a gene segregate from each other
into the gametes during anaphase I of meiosis.
3
Dihybrid cross
• F2 generation contained both parental types and recombinant types.
• Alleles of genes assort independently, and can thus appear in any
combination in the offspring.
Mendel’s genetics - the classic
Law of Independent Assortment
• During gamete formation different pairs of alleles
segregate independently of each other
4
Test cross:
Way to find unknown genotype
Chromosome Theory of Inheritance
• The chromosome theory correlates Mendel’s laws
with chromosome behavior during meiosis
• Specific traits are transmitted with specific
chromosomes
• T.H. Morgan’s experiments demonstrating sex-linked
inheritance of a gene determining eye-color
demonstrate the transmission of traits with
chromosomes
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Morgan’s cross
Reciprocal cross
gives different results
X- linked inheritance
P
X
+/Y
w/w
F1
w/Y
w/+
All white flies are male
Eye color is on X chromosome
From Cailin Joyce
6
Mitosis vs. Meiosis
Let's see it in motion!
Mitosis vs. Meiosis
Summary
Occurs in
# of Division
Homologous
chromosome
pair/Recombination
Produces
Genetic makeup
relative to a parent
cell
Mitosis
Somatic cells
One round
Meiosis
Germ cells
Two rounds
NO
YES
Two diploid
daughter cells
Four haploid
daughter cells
identical
different
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Crossovers in Meiosis
Crossing over in prophase I:
Essential for normal disjunction of homologs in meiosis I
Pearson Educ.
Exception to Mendel’s Law
• Dominance
• Lethal genes
• Pleiotropy
Single mutant gene resulting in multiple different phenotypes
e.g. S allele of sickle cell anemia
• Linkage
Genes that are physically close to one another on the same
chromosome tend to be inherited together
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Dominance
• Partial (Incomplete) Dominance
Alleles are not completely dominant to each other.
Heterozygote phenotype is intermediate to two homozygotes
(e.g. red petal allele + white petal allele = pink petal phenotype)
• Co-Dominance/ multiple allele
Heterozygote has phenotype of both homozygotes
(e.g. ABO blood types, Histocompatibility)
• Haploinsufficiency
Normal gene function requires more than 50% of fully active gene
product (exception to loss of function ⇒ recessive )
Lethal allele
Meet Stubbin…
The expected Mendelian ratio from the
mating of two heterozygous Manx cats is
3 Manx:1 WT.
The actual ratio from the mating of two
Manx cats is 2 Manx:1 WT.
M
m
M = Manx allele
M MM Mm
m = wild type allele
m Mm
mm
From Cailin Joyce
9
More definitions
Epistasis
One gene masks phenotype of another gene
Penetrance
% of individuals with a genotype that display a phenotype
Expressivity
The degree to which the phenotype is displayed
among individuals of a given genotype
Complementation(cis/trans) Testing
M1 and m2 are two separate recessive haplosuffcient mutations of Unc
If Unc phenotype, 2 mutations fail to complement
⇒ are alleles of the same gene (cis configuration)
If WT phenotype, 2 mutations complement
⇒ are alleles different genes (trans configuration)
Wormbook
10
Yeast Terminology
12 MB genome, 16 chromosomes (I, II, III,….,XVI)
MATa and MATα mating types
Naming loss of function (lf) phenotype
Wild type gene all caps -- LEU2
Mutant gene lowercase, italic or underline. “Δ” is full
deletion, “::” indicates insertion cassette -- leu2
Alleles of same gene dash and numbered after gene
name. Temperature sensitivity with “ts”, “cs”
superscript
Protein “p” after wild type gene name -- Leu2p or
LEU2p
YJF4561 MATa ura3-52 leu21ts trp163Δ mlh1::hisG
Yeast Terminology, cont.
Systematic gene names:
YBR304C
C=Crick strand
W=Watson strand
yeast
B=chr II,
C=III…
P=XVI
#=ORF number
R=right arm,
L=left arm
Strain names:
yeast
YJF4561
#=strain number
PI initials, e.g Justin Fay
S228C is canonical/reference lab strain
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Yeast Life Cycle
mitosis
a/α diploid
haploids
a
meiosis
sporulation
α
mitosis
tetrad
a
α
a
α
ascus
MATa and MATα haploids respond to a factor secreted by the opposite
mating type. a and α haploids cannot sporulate
C.elegans Terminology
100 MB genome, 6 chromosomes (I, II, III,…V, X)
(aka linkage groups)
Hermaphrodite = XX, Male = XO
Holocentric chromosomes
Gene Naming after lf phenotype italic lowercase unc-1
Wild type gene unc-1(+) or unc-1
Mutant gene unc-1 (-) or unc-1(e78) : (originating lab)
Alleles of same gene parentheses after gene name,
letters indicate originating lab. Temperature
sensitivity following allele name
Protein all capital -- UNC-1
Phenotype Unc-1 first letter capital
DG1647 [efn-2(ev658ts)IV, fog-2(q71)V; ceh-18(mg57)X]
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C. Elegans Life Cycle
Bristol N2 is canonical/reference strain
Drosophila Terminology
175 MB genome, 4 chromosomes ((X), I, II, III, IV)
IV is small and heterochromatic, mostly ignored in genotypes
Female = XX, Male = XY
Gene Naming lf phenotype with lots of creative license
Wild type gene lowercase, italicized; with a + (or just a +) -hh+
Mutant gene lowercase (if recessive), italic or underline -hh
Alleles of same gene superscript (if superscript “D” =
dominant mutation). Temperature sensitivity probably
within superscript
Protein same as gene name, in caps (or 1st letter
capitalized). No italics -- Hedgehog or HH
wgSp-1/CyO; ry506 P{GawB}wts1 Df(3R)P14/TM6
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Drosophila Terminology, cont.
Polytene chromosomes
I: #1-20, IIL: #21-40, IIR: #41-60,
IIIL: #61-80, IIIR: #81-100
each # subdivided into A-F
Recombination absent in males
Balancers
Multiple inversions (no recombination)
Dominant mutation with easily visible phenotypes
FM7: bar eye marker
SM5: curly wing marker (CyO also 2nd chr marker)
TM3: stubble bristle marker
lethal mutation
Drosophila Life Cycle
14
Mouse Terminology
2.5 GB genome, 20 chromosomes (1,2,3,…19, X/Y)
Female = XX, Male = XY
Gene Naming generally named for homologs in other
species, other family members, lf phenotype, or
disease associations
Wild type gene first letter upper case, other lower
case; italicized -- Fgf4
Mutant gene same as wt
Alleles of same gene superscript, named by labs -Fgf4tm1.1Mrc
Protein upper case, no italics -- FGF4
C57BL/6J Msx2-cre, Fgf9-/-, Fgf17-/- ; Fgf4flox/flox
Human Terminology
3 GB genome, 23 chromosomes (1,2,3,…22, X/Y)
Female = XX, Male = XY
Gene Naming generally named for homologs in other
species, other family members, or disease
associations
Wild type gene all caps, italicized, no hyphens -GATA3
Mutations specific change or polymorphism listed
after gene name. -- GATA3 L533A, GATA3 -815A/G
Protein all caps, no italics -- GATA3
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Human Terminology, cont.
Unknown ESTs letters indicate lab/center/chromosome
of origin e.g. KIAA3513, MGC35235, C2ORF1
P arm
Gene loci 7q31.2 = CFTR gene
centromere
chromosome 7
long arm (p=small arm)
Q arm
region 31, subregion 2 (defined by
banding patterns or genetic linkages)
Human Pedigrees
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