Transmission Genetics: Heritage from Mendel 2. Mendel’s Genetics Experimental tool: garden pea...
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Transcript of Transmission Genetics: Heritage from Mendel 2. Mendel’s Genetics Experimental tool: garden pea...
Mendel’s Genetics• Experimental tool: garden pea• Outcome of genetic cross is independent
of whether the genetic trait comes from the male or female parent
• Reciprocal genetic crosses produce the same results
• Many human traits follow this pattern of inheritance
Mendel’s Experiments • Gene : inherited trait• Plants with different
forms of a trait, such as yellow vs. green seeds(alleles) were genetically crossed
• Mendel counted the number of offspring with each trait (F1), (e.g.: green seeds)
• He crossed F1 plants among themselves and counted F2 offspring
Mendel’s Observation
• Genetic cross between parents that “breed true” for a pair of traits, round seeds vs. wrinkled seeds, produces offspring with round seeds only (F1)
• Round seeds are dominant • Each parent has two identical copies of
the genetic information specifying the trait (homozygous) and contributes one in each cross (P1)
Mendel’s Hypothesis
• Round seed parent “AA” = genotype
• Wrinkled seed parent
“aa” = genotype• Round seed parent contributes “A”
gamete to offspring• Wrinkled seed parent contributes “a”
gamete to offspring
Law of Dominance
• Offspring genotype = A + a = Aa heterozygous
• All offspring produce round seeds although they are genetic composites of “Aa” because “A” (round) is dominant to “a” (wrinkled)
Law of Segregation
• F1 genotype =“Aa”= monohybrid• “Aa” parent produces either “A” or “a”
gametes in equal proportion
Law of Segregation
(simple consequence of two chromosomes)
Monohybrid Genetic Cross
• Genetic cross : Aa X Aa produces A and a gametes from each parent
• Punnett square shows four possible outcomes = AA Aa, aA, and aa
• Three combinations = AA, Aa, and aA produce plants with round seeds and display a round phenotype
• Fourth combination = aa displays wrinkled phenotype = recessive
Monohybrid Genetic Cross
C h art T it le : M on oh yb rid g en e tic C ross
1 /4A A
rou n d seed sd om in an t
1 /2A a
rou n d seed sd om in an t
1 /4aa
w rin k led seed srecess ive
P aren ts : A a X A ag am etes : A o r a
each p aren t p rod u ces A an d a g am etes an d con trib u tes on e g am ete a t fe rt iliza tion
Mendelian Ratios
• Genotypic ratios differ from phenotypic ratios since dominant phenotype consists of AA” and “Aa”
• F2 results of monohybrid cross show 3:1 round:wrinkled phenotypic ratio
• Genotypic ratios of monohybrid cross are 1:2:1 = 1/4 AA + 1/2 Aa + 1/4 aa
Testcross Analysis
• Testcross analysis allows geneticist to determine whether observed dominant phenotype is associated with a homozygous “AA” or heterozygous “Aa” genotype
• Genetic cross is performed using a recessive testcross parent = “aa”
Testcross Results
• AA + aa = Aa ; dominants only
parent homozygous
• Aa + aa = 1/2 Aa + 1/2 aa
produces 1/2 dominant, 1/2 recessive parent heterozygous
Dihybrid Cross Ratios
• two different phenotypic traits, such as seed color (yellow vs. green) and
seed shape (round vs. wrinkled) • Analysis of all combinations: (3:1 round :
wrinkled and 3:1 yellow : green) produces 9:3:3:1 phenotypic ratio (round/yellow : round/green : wrinkled/yellow : wrinkled/green
Law of Independent Assortment
• Combinations of individual elements within dihybrid pair generate genotypic ratios for dihybrid cross
• True for any number of unlinked genes• Also a consequence of distinct
chromosomes
Dihybrid Testcross
• WwGg gametes = WG + wG +Wg + wg = 1:1:1:1 ratio;
• double recessive gametes = wg• Offspring = WwGg + wwGg + Wwgg +
wwgg = 1:1:1:1 ratio• Testcross shows that parent is
heterozygous for both traits (dihybrid)
Trihybrid Genetic Cross
• Trihybrid cross = three pairs of elements that assort independently, such as WwGgPp
• For any pair phenotypic ratio = 3:1• For two pairs ratio = 9:3:3:1• Trihybrid: 27:9:9:9:3:3:3:1
Probability Rules
• Addition Rule: The probability of obtaining one or the other of two mutually exclusive events is the sum of their individual probabilities
• Multiplication Rule: The probability of two independent events occurring simultaneously equals the product of their individual probabilities
Mendelian Probabilities
• Dihybrid crosses also follow sum rule and product rule to determine outcome probabilities
• Phenotypic outcome = 9:3:3:1
• Genotypic outcome = 1:2:1:2:4:2:1:2:1
Pedigree Analysis• In humans, pedigree analysis is used to
determine individual genotypes and to predict the mode of transmission of single gene traits
• To construct a pedigree, the pattern of transmission of a phenotypic trait among individuals in a family is used to determine whether the mode of inheritance is dominant or recessive
• Pedigree analysis is used to study single gene disorders, such as Huntington’s Disease, a progressive neurodegenerative disorder
Pedigree Analysis: Dominance• Dominant phenotypic traits usually appear in
every generation of a pedigree
• About 1/2 the offspring of an affected individual are affected
• The trait appears in both sexes if the gene is not on the X chromosome
Dominant Single Gene Disorders
Tran sm iss ion P rob ab ilit ies fo r D om in an t S in g le G en e Tra its
A aa ffec ted h e te rozyg o te
p rob = 1 /2A = d e fec tive g en e tic e lem en t
aan on affec ted recess ive
p rob = 1 /2a = n on a ffec ted g en e tic e lem en t
m os t com m on c rossA a X aa
A a = a ffec tedaa = n on a ffec ted
Pedigree Analysis: Recessive
• Pedigree analysis can used to distinguish dominant vs. recessive modes of inheritance for traits determined by single genes
• Analysis of patterns of transmission of recessive genes is used to identify carriers of recessive traits which cannot be determined by direct phenotypic analysis
• Recessive traits occur in individuals whose parents are phenotypically dominant
Inheritance of Recessive Genes
• Two phenotypically dominant people who produce a child with a recessive genetic disorder: 1/4 probability that any of their children will be affected and 1/2 that they will be carriers
Recessive Genetic Disorders
In h eritan ce o f R ecess ive S in g le G en e D isord ers
A Ap rob = 1 /4
n on affec ted
A ap rob = 1 /2
carrie r
aap rob = 1 /4
a ffec ted
m os t com m on c rossA a X A a
A = n on a ffec ted g en ea = a ffec ted g en e
Incomplete Dominance
• Heterozygote phenotype is intermediate between dominant and recessive phenotypes (snapdragons)
• F1 of cross between dominant (red) and recessive (ivory) plants shows intermediate phenotype (pink)
• F2 products show identical phenotypic and genotypic ratios
Multiple Alleles/Co-dominance
• For some traits more than two alleles exist in the human population
• ABO blood groups are specified by three alleles which specify four blood types
• ABO blood group inheritance also illustrates principle of co-dominance in which both alleles contribute to the phenotype in the heterozygote
• Antibodies are proteins which bind to stimulating molecules = antigens
Multiple Alleles/Co-dominance• IA and IB are dominant to IO, genotype AIO =
type A; IBIO = type B
• IA and IB are co-dominant; each allele specifies antigen: genotype IAIB = type AB
• IO = is recessive genotype IOIO
Biochemical Genetics
• Many recessive genes code for enzymes which carry out specific steps in biochemical pathways
• Mutations which alter the structure of genes block enzyme production if both copies of the gene are defective
• Disorders were termed “inborn errors of metabolism” by Garrod
Biochemical Genetics• Recessive genes often
contain mutations which block the formation of gene product (ww)
• Heterozygotes which contain one recessive gene copy (Ww) may produce only 1/2 the amount of protein specified by the homozygous dominant (WW) which contains two functional copies of the gene
Biochemical Genetics
• Heterozygotes (Ww) may still produce sufficient gene product to display dominant phenotype = round seed; genotype = carrier
• For some genes reduction of gene product by 1/2 in the heterozygote may be physiologically significant, especially for structural proteins = dominant disorders
Biochemical Genetics
• Variable expressivity refers to genes that are expressed to different degrees in different individuals, e.g.: severity of an inherited disease
• Incomplete penetrance means that the phenotype predicted from a specific genotype is not always expressed, e.g.: individual inherits mutant gene but shows no effect
Genetic Epistasis• Epistasis alters Mendelian
9:3:3:1 phenotypic ratios in dihybrid inheritance
• In epistasis, two sets of genetic elements interact to produce a single phenotype, which modifies the observed phenotypic ratios
• Mendelian pattern of inheritance
Genetic Complementation• Complementation tests are used to determine if
different phenotypes result from variations in one gene
• Homozygous recessive genotypes which are genetically crossed can only produce a dominant phenotype if the recessive genetic elements are located on different genes
Genetic Complementation
• A mutant screen is an experiment which generates mutations which affect specific phenotypes
• Multiple alleles refer to the various forms of a gene
• Wildtype refers to the phenotype for a specific trait most commonly observed
Genetic Complementation
• The complementation test groups mutants into allelic classes called complementation groups
• Lack of complementation = two mutants are alleles of the same gene
• Principle of Complementation: two recessive allelic mutations produce mutant phenotype; two non-allelic recessive mutations show no effect