beyond mendelism
DESCRIPTION
GeneticsTRANSCRIPT
![Page 1: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/1.jpg)
Beyond Mendelism
![Page 2: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/2.jpg)
![Page 3: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/3.jpg)
Fig. 12.1 Allelic forms of a gene
![Page 4: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/4.jpg)
1. Single-gene inheritance :a. Deviations from complete dominance and recessiveness
b. Multiple alleles
c. One gene determine more than one trait
2. Multifactorial inheritance
Extension to Mendel
![Page 5: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/5.jpg)
Deviations from complete dominance and recessiveness
![Page 6: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/6.jpg)
Fig. 3.3
Incomplete dominance
![Page 7: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/7.jpg)
CodominanceF1 hybrid display the traits of both parents
![Page 8: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/8.jpg)
spotted dotted
![Page 9: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/9.jpg)
Multiple allelesComplete set of known alleles of one
gene is called an allelic series
![Page 10: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/10.jpg)
Fig. 3.5
ABO blood types are determined by three alleles of one gene
![Page 11: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/11.jpg)
Fig. 3.6
Establishing thedominance relationsbetween multiple alleles
![Page 12: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/12.jpg)
Mutations are the source of new allelesWild-type allele: frequency more than 1%
Mutant allele: frequency less than 1%
Monomorphic(One wild-type allele)
ABO blood type: polymorphic
agouti
black/yellowblack
![Page 13: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/13.jpg)
![Page 14: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/14.jpg)
![Page 15: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/15.jpg)
Two alleles with recessive lethal Recessive lethal alleles
![Page 16: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/16.jpg)
Table 3.1
![Page 17: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/17.jpg)
Sickle-cell anemia
Mutant -globin aggregates to form long-fiber
Pleiotropy
![Page 18: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/18.jpg)
Pleiotropy of sickle-cell anemia: dominance relation vary
Cells break down
Oxygen drops
![Page 19: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/19.jpg)
Phenotype at level of expression of anemiaHbA is dominant
![Page 20: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/20.jpg)
Phenotype at cell shape level
HbA/HbA Normal shape
HbS/HbS Sickled
HBS/HbA Partially sickled***
High altitudes: HbA & HBs are incompletely dominant
Se level: A dominant
Phenotype at protein level
At this molecular level, alleles HbA and HBs are codominant
![Page 21: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/21.jpg)
Phenylketonuria (PKU)
![Page 22: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/22.jpg)
Phenylketonuria• Autosomal recessive disease- single gene disease• Defective allele of gene coding for liver enzyme
phenylalanine hydroxylase (PAH)• Phe in diet converted into phenylpyruvic acid,
transported to brain via bloodstream • Impedes normal development, mental retardation• Many mutations at different sites (allelic series):
Near active site (null) or away from it with residual function (leaky)– Normally functioning wild type (P)
– All defective recessive mutations, null and leaky (p)
![Page 23: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/23.jpg)
Phenylketonuria• Underlying complexity of genetic system
involved:• Some cases of elevated phenylalanine level and
its symptoms: Not associated with PAH locus (other genes involved)
• Some cases: People with PKU (elevated phenylalanine) no abnormal cognitive development
• Hence involvement of other genes + environment (gene for tetrahydrobiopterin synthesis)
![Page 24: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/24.jpg)
Phenylketonuria• Many steps in pathway from Phe ingestion to
impaired cognitive development– Amount of Phe in diet– Transportation of Phe to appropriate sites in
liver– Liver: PAH + cofactor, tetrahydrobiopterin – To affect cognitive development: Excess
phenylpyruvic acid must be transported to brain via bloodstream, pass through BBB
– Inside brain: Developmental processes must be susceptible to action of phenylpyruvic acid
![Page 25: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/25.jpg)
![Page 26: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/26.jpg)
Multifactorial InheritanceInteraction of genes
Identifying the interacting genes that contribute to a particular biological property
1. Treat cells with mutagens (UV): Set of mutants with abnormal expression of property under study
2. Test the mutants to determine how many gene loci are involved, which mutations are alleles of same gene
3. Combine mutations pairwise by means of crosses to form double mutants to see if they interact (gene product interaction). Specific ratio of progeny
![Page 27: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/27.jpg)
Complementation
• Harebell: Blue WT, three white-petaled mutants, homozygous pure-breeding strains $, £, and ¥
• Phenotypically alike, genetically identical ?
• Mutant condition determined by recessive allele of a single gene
![Page 28: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/28.jpg)
Harebell plant (Campanula species)
![Page 29: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/29.jpg)
Are they three alleles of one gene, or of two genes, or of three genes?
Check for complementation
![Page 30: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/30.jpg)
Interaction of genes1. Complementation:• Production of a wild-type phenotype when two
recessive mutant alleles are brought together in the same cell
• Complementation test: By intercrossing two individuals that are homozygous for different recessive mutants
• Observe whether progeny have wild-type phenotype– If recessive mutations are alleles of same gene: no
wild-type progeny
![Page 31: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/31.jpg)
Complementation
• Two recessive mutations in different genes wild-type function provided by respective wild-type alleles
• Cross F1 dihybrid plants• F2 9:7 (blue:white)
– modification of the dihybrid 9 :3:3:1
• Complementation is a result of cooperative interaction of wild-type alleles of two genes
![Page 32: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/32.jpg)
![Page 33: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/33.jpg)
• Plant will have white petals if it is homozygous for the recessive mutant allele of either gene or both genes
• Blue phenotype: At least one dominant allele of both genes (both are needed to complement each other and complete sequential steps in the pathway)
• Three of genotypic classes will produce same phenotype, so overall only two phenotypes result. Different steps in a biochemical pathway
![Page 34: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/34.jpg)
Homozygous mutation
Theoretical notation
Cross between
F1 Enzyme 2 functional but no substrate
Other crosses: wild-type alleles for both enzymes
![Page 35: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/35.jpg)
Three phenotypically identical whitemutants—$, £, and ¥—are intercrossed
Mutations in the same gene (such as $ and £) cannot complement, because the F1 has one gene with two mutant alleles. Pathway is blocked and flowers are white
![Page 36: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/36.jpg)
When mutations are in different genes (suchas £ and ¥), complementation of wild-type alleles of each gene occurs in F1 heterozygote. Pigment is synthesized and flowers are blue
![Page 37: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/37.jpg)
Complementation: Gene interaction from different pathways
• Inheritance of skin coloration in corn snakes• Natural color: Repeating black and orange
camouflage pattern• Orange pigment: o+ (presence of orange
pigment) and o (absence of orange pigment).• Black pigment: b+ (presence of black pigment)
and b (absence of black pigment).
![Page 38: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/38.jpg)
Genotypes
• Natural: o+/– ; b+/–.• Black: o/o ; b+/–• Orange: o+/– ; b/b• Albino: o/o ; b/b
![Page 39: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/39.jpg)
![Page 40: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/40.jpg)
Independence of interacting genes 9:3:3:1
![Page 41: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/41.jpg)
![Page 42: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/42.jpg)
Epistasis• Ability of a mutation at one locus to override a mutation
at another in a double mutant• When a mutant allele of one gene masks expression of
alleles of another gene and expresses its own phenotype– Overriding mutation: epistatic– Overridden mutation: hypostatic
• Genes in same cellular pathway
• Epistatic mutation of gene earlier in pathway than that of hypostatic
![Page 43: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/43.jpg)
White (w/w) Magenta (m/m) unlinked
WT
9:3:4= Epistasis, white epistatic to magenta
Petal pigment synthesis in blue-eyed Mary (Collinsia parviflora)
![Page 44: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/44.jpg)
![Page 45: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/45.jpg)
![Page 46: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/46.jpg)
![Page 47: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/47.jpg)
(a) Rose (b) pea (c) walnut (d) single
Domestic chickens comb shapes
![Page 48: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/48.jpg)
Comb shape: Two independently assorting genes (R and P) each with two alleles
Wyandotte chickens: Rose combs (RRpp)
Brahma chickens: Pea combs (rrPP)
F1 hybrids: Walnut (RrPp)
F2: of 9:3:3:1 walnut:rose:pea:single
![Page 49: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/49.jpg)
Figure 4.17b
The crosses of Bateson and Punnett
![Page 50: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/50.jpg)
Fig. 3.13
Epistatic: the effect of one gene hides the effect of the other gene
Recessive epistasis
Addition of A or B sugars
H allele is epistatic to the I gene
![Page 51: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/51.jpg)
Suppressors
• Suppressor: Mutant allele of one gene that reverses effect of a mutation of another gene, resulting in a wild-type or near wild-type phenotype• Use a mutant, expose to mutagen and screen descendents for WT
Difference from epistasis:
• Suppressor cancels expression of a mutant allele and restores corresponding wild-type phenotype• Two phenotypes segregateF2 ratio: 13:3
![Page 52: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/52.jpg)
Red: WT
Pd: Purple
su suppressespd (red WT)
Pd+ (Red)Pd/su (Red)Pd (Purple)
![Page 53: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/53.jpg)
Penetrance & Expressivity
Penetrance: percentage of individuals with a given allele who exhibit the phenotype associated with that allele
Expressivity measures degree to which a given allele is expressed at phenotypic level (intensity of phenotype)
![Page 54: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/54.jpg)
![Page 55: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/55.jpg)
Penetrance & Expressivity
Reasons for not expressing trait:1.Influence of environment: Phenotype of
mutant individual raised in one set of circumstances may match phenotype of a wild-type individual raised in a separate set of circumstances
2. Influence of other genes: Modifiers, epistatic genes, or suppressors in rest of genome may act to prevent expression of typical phenotype
![Page 56: Beyond Mendelism](https://reader034.vdocuments.mx/reader034/viewer/2022042814/552b75394a7959a5588b465f/html5/thumbnails/56.jpg)