Download Ch04 Extensions of Mendelian Genetics

Chapter 4
Modification of Mendelian Ratios
Beyond Mendel…
• Since Mendel’s work was rediscovered in
the early 1900’s:
• Researchers have studied the many ways genes
influence an individual’s phenotype
• These investigations are called neo-Mendelian
genetics (neo from Greek for “new”)
• Chapter 4 examines types of inheritance
observed by researchers that did not conform to
the expected Mendelian ratios
Extensions of Mendelian Genetics
Alleles 等位基因
• Alleles are alternate forms of the same gene
• How alleles affect phenotype
– Not always simple dominant/recessive issue
• Gene interaction
– Phenotype controlled by more than one gene
• Sex-linked genes (X-linkage in X/Y
organisms)
• Phenotype can depend on more than
genotype
– The allele occurring most frequently in a
population (the “normal” allele) is called the
wild-type (wt) allele（野生型）
– Wt allele is usually dominant and is expressed
as the wild-type phenotype
– Wt allele used as “standard” for comparison of
all mutations（突变） (alternative alleles) of
the gene/locus
– Environmental effects
孙加焱, 涂进东, 范叔味, 吴建国, 石春海. 甘蓝型油菜理化诱变和突变体库的构建. 遗传, 2007, 29(4): 475-482.
γ 射线与甲基磺酸乙酯（EMS）溶液复合处理种子
a wild-type Arabidopsis
inflorescence
a apetala1 mutant
Arabidopsis inflorescence
无花瓣突变体
苗期子叶性状变异 The mutants of cotyledon traits in seedling
a: 浅绿色子叶变异(右)与野生型; b: 黄化子叶变异(右)与野生型; c: 无子叶变异;
d: 三子叶变异; e: 四子叶变异; f: 喇叭形子叶变异;
g: 多耳突子叶变异。
http://serc.carleton.edu/genomics/units/arabidopsis.html
1
孙加焱, 涂进东, 范叔味, 吴建国, 石春海. 甘蓝型油菜理化诱变和突变体库的构建. 遗传, 2007, 29(4): 475-482.
Mutations 突变
• Mutation
– Ultimate (最终的) source of new alleles
– Genetic information is modified
• often (not always) produces altered gene product（基因
产物）
叶部性状变异 The mutants of leaf traits
a: 深绿叶色变异(下)与野生型; b: 浅绿叶色变异(下)与野生型; c: 黄化变异(下)与野生
型; d: 嵌合黄化; e: 薹叶形变异(下)与野生型; f: 皱缩叶变异; g: 卷叶变异(下)与野生
型; h: 大叶片变异(下)与野生型; i: 宽圆叶变异(下)与野生型。
– New phenotypes result from changes in functional
activity of gene product
• Eliminating（去除）enzyme（酶）function
• Changing relative enzyme efficiency
• Changing overall enzyme function
– e.g. enzyme specificity
Allele Symbols 等位基因符号标识
• For simple Mendelian traits:
Drosophila Conventions (cont.)
• 1st letter of recessive form
• Lowercase（小写字母）= recessive allele（隐性等位基因）
• Uppercase（大写字母）= dominant allele（显性等位基因）
• Other systems: Drosophila（果蝇）
• Use 1st letter of mutant allele (or combination of 2 or 3
letters) to name all alleles at this locus
• If trait is recessive, use lowercase; uppercase if
dominant
• Wild-type is indicated by the same letter (s), but with a
superscript（上标） “+” (e.g. Wr and Wr + for
wrinkled and wt wing alleles), or when using /, Wr/+
for heterozygote
More Conventions…
• The Drosophila system can be applied to other
organisms as well:
• When no allelic dominance, uppercase letters and
superscripts designate alternate alleles
• R1 and R2, LM and LN
• There are other systems of genetic nomenclature
（命名法）:
• leu - for bacteria with mutation blocking leucine（亮
氨酸）biosynthesis
• BRCA1 for a human gene associated with inheritied
risk of breast cancer
• Example: body color
•
•
•
•
•
•
•
Ebony mutant phenotype is indicated by e
Normal gray (wild-type) is indicated by e+
Three possible genotypes:
e+/e+ : gray homozygote (wild type)
e+/e : gray heterozygote (wild type)
e /e : ebony homozygote (mutant)
Or the above could be simple +/+; +/e and e/e
Incomplete Dominance 不完全显性
• Cross between two parents with contrasting
traits（相对性状）
• Offspring with an intermediate phenotype（中间型）
• incomplete or partial dominance （不完全/部分显性）
• Example: red snapdragon crossed with white
snapdragon （金鱼草）
• F1 offspring have pink flowers
• F2 generation (Fig. 4.1), ¼ are red, ½ are pink, and
¼ are white
• Note: phenotypic and genotypic ratios are the same
• Each genotype has its own phenotype
2
Incomplete
Dominance
Codominance 共显性
• Codominance
• two alleles at a locus produce different and
detectable gene products in heterozygote
• No dominance or recessiveness
• No “blended” （混合的）phenotype (not
incomplete dominance)
• red x white P1 generation
– pink F1
– 0.25/ 0.50/ 0.25 ratio of
red/ pink/ white in the F2
generation
• Example: MN blood group in humans
• Red blood cell glycoprotein surface antigen
has two forms (M and N)
• An individual may exhibit either or both
Multiple Alleles 复等位基因
Codominant marker 共显性标记
Bb
F1
• Individuals can have up to two alleles for a single
gene (diploid, homologous chromosomes)
• Multiple alleles applies when there are three or
more alleles of the same gene in a population
bb
P2
• Any gene can be modified in multiple places/ways,
SNP
BB
bb
Bb
• each unique change produce a different allele (but not
necessarily different phenotype)
BB P1
• NOTE: multiple alleles studied in populations, not
individuals
• Classic example is human ABO blood groups
ABO Blood Groups
• Human ABO blood groups provide example of a
multiple allele situation
• A and B antigens（抗原）present on surface of
blood cells (similar to MN blood group antigens)
• A and B antigens controlled by gene on chromosome 9
• By 1924, studies of blood types of many families
suggested that 3 alleles of a single gene were
responsible for ABO phenotypes
Review of ABO blood groups
• Phenotype of individual determined by mixing
blood sample with antiserum（抗血清）
containing type A or type B antibodies（抗体）
• Four possible phenotypes:
•
•
•
•
Person has A antigen only (A phenotype)
Person has B antigen only (B phenotype)
Person has both antigens (AB phenotype)
Person has neither antigen (O phenotype)
3
Multiple Alleles
The Human Blood Groups
Phenotype Genotype
Antigen (present on
red blood cells)
Antibody (found in
the serum)
O
ii
None
anti-A and anti-B
A
B
IAIA, IAi
IBIB, IBi
A antigen
B antigen
anti-B
anti-A
AB
IAIB
Both A and B antigens
None
Lethal Alleles 致死基因
• Many gene products are essential to survival of
an organism
– Lethal alleles represent “essential genes”, lethal in
homozygous state
• Time of death is dependent upon when the gene
product is essential to development
– Loss of function alleles can be recessive lethal (often
are)
• Heterozygotes may tolerate a non-functional mutant
allele if wt allele produces sufficient product for
organism survival
• Sometimes recessive lethal are still dominant with
respect to phenotype
Dihybrid
cross with
two loci
having
different
patterns of
inheritance
• Although ABO blood types in humans is
considered a classic example of multiple
alleles, most all loci exhibit this
phenomenon
– Eye color locus for Drosophila (Morgan’s
famous white-eyed mutant) has over 100
known alleles
Crosses of Two Gene Pairs with
Different Modes of Inheritance
• E.g. autosomal（常染色体的 ）recessive locus
with a codominance locus
• Remember: although the 9:3:3:1 ratio will be
altered, all unlinked loci will still follow
Mendel’s principle of independent assortment…
• Regular Punnett square and determine
phenotypes individually or forked method
Epigenesis 后成说，渐成论
• Many phenotypes affected/controlled by more
than one gene
– “gene interaction” (occurs at many levels for many
reasons)
• Epigenesis
– Development is a cascade（一连串）of events
– Each ensuing step of development increases the
complexity of the organ and is under the
control/influence of many genes
4
Floral transition genes in Arabidopsis thaliana and
homologous EST, cDNA and genomic sequences in B. vulgaris
Vernalization
PAF1
complex
VIP4
• Epistasis
MSI1
VIN3
ELF8
– The effect of one gene pair (locus) masks or modifies
the effect of another gene pair
VRN2
ELF7
FLD
ELF3
Circadian clock
LHP1
PIE1
+
VIP3
FVE
Autonomous
pathway
AGL19
VRN1
EFS
LHY/CCA1
FRL1
CZS
+
CO+
FLC
FCA
FPA+
GI+
FKF1
FLK+
SOC1
FT
FD
AP1
CAL
FUL
Long days
Light quality
Photoperiod pathway
CDF1
BRM
FY
PHYs
CRYs
TOC1
2
1
LD+
ZTL
FRI
SWP1
PFT1
Floral integrators
3
GA2ox2
TFL1
MYB33
3
GA
GA3ox1
LFY
3
GA20ox1
RGA
Epistasis 上位性
SPL3-5
Floral meristem
identity genes
GAI
• Examples
– Recessive alleles at one locus override expression of
alleles at another locus. Alleles at 1st locus are said to
be epistatic to the masked hypostatic（下位的）alleles
at the 2nd locus
– Allele(s) at one locus may require specific allele at
another locus, these pairs are said to complement（互
补）each other
• The FUTI allele and ABO phenotype is an
example of epistasis
Activation
Repression
1
Reeves et al. (2007)
2
Chia et al （2008）
Fruit Shape in Summer Squash
• Disk-shaped fruit (AABB) crossed with long
fruit (aabb)
• F1 is all disc-shaped fruit
• F2 includes both parental phenotypes plus
spherical variants in 9:6:1 ratio
– 9/16 A-B- disc
– 3/16 A-bb sphere, 3/16 aaB- sphere（球形）
– 1/16 aabb long
– Disc requires dominant alleles at both loci, sphere
requires a dominant allele at one/either locus and no
dominant alleles at either locus give long
Modified Dihybrid F2 Ratios
Modified Ratios
• Note that although many ratios are possible
for the dihybrid crosses, in all cases
segregation（分离）and independent
assortment（独立分配）rules are not
violated
• Genotypic ratios remain the same and
therefore phenotypic ratios expressed in
1/16ths as before
• What changes is how you convert
genotypes to phenotypes
5
Pleiotrophy 一因多效
• One gene has effect(s) on multiple phenotypes
• Many examples
Nature Genetics, 2008, 40, 761 - 767.
- 樱草中由一个隐性基因可以决定花的样式
和花柱的长短
- Ghd7 in rice
Chromosome-based Sex Determination
Human Karyotype
（人类染色体核型）
• X,Y system used for sex determination by many
animal and plant species
– X is a large chromosome and encodes many genes
– Y is a small chromosome with few genes (not
homologous to X in the traditional sense but has
pairing region for synapsis 联会)
– Males therefore have a single copy of genes encoded
by the X chromosome, hemizygous（半合子）
• These genes have unique inheritance/expression
properties resulting from their “X-linkage”
Figure 1-3
X-linkage in Drosophila
• First documented by Thomas Morgan, 1910
– White-eyed mutant
– Inheritance pattern clearly related to sex of
parent carrying allele and offspring
– See figure 4-11
Copyright © 2006 Pearson Prentice Hall, Inc.
X-linkage and Humans
• Many traits controlled by X chromosome-linked
traits
– Red/green color blindness（色盲）is classic example
– Numerous significant genetic-based diseases
– Only females are carriers of recessive alleles
• Males（XY，男性）are hemizygous
6
Pedigree
Environmental Effects
• Temperature effects
– Evening primrose produces red flowers at 23℃ and
white flowers at 18℃
– Siamese cats and Himalayan rabbits have darker fur on
cooler areas of body (tail, feet, ears)
Likely Genotypes
• Enzymes lose catalytic function at higher temperature
• Temperature sensitive mutations
– Mutant allele only expressed (phenotype) at [generally]
lower temperature
– ts phage mutants, restrictive and permissive
temperatures
• Heat-shock genes
Nutritional Effects
• Nutritional mutations
– Prevent synthesis of nutrient molecules
– Auxotrophs
– Phenotype expressed or not depending upon the diet
• Phenylketonuria（苯酮尿症）
– Loss of enzyme to metabolize phenylalanine
– Severe problems unless low Phe diet
• Galactosemia (very bad again) and lactose
intolerance (unpleasant)…
7