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Transcript of Human Genetics Mendelian Genetics.
Human Genetics
Mendelian Genetics
Inheritance Parents and offspring often
share observable traits. Grandparents and
grandchildren may share traits not seen in parents.
Why do traits disappear in one generation and reappear in another?
Why do we still keep talking about Mendel and his peas?
Darwin Prior to MendelScientists looked for rules to explain continuous
variation.The “blending” hypothesis: genetic material from
the two parents blends together Head size, height, longevity – all continuous
variations - support the blending hypothesisThe “particulate” hypothesis: parents pass on
discrete heritable units (genes)Mendel’s experiments suggested that inherited
traits were discrete and constant
Gregor Mendel
Why did Mendel succeed in seeing something that nobody else saw?
1. He counted2. Chose a good system3. Chose true-breeding characters
http://www.mendel-museum.org/eng/1online/experiment.htm
The field of genetics started with a single paper!
Mendel is as important as Darwin in 19th century science
Mendel did experiments and analyzed the results mathematically. His research required him to identify variables, isolate their effects, measure these variables painstakingly and then subject the data to mathematical analysis.
He was influenced by his study of physics and having an interest in meteorology. His mathematical and statistical approach was also favored by plant breeders at the time.
Mendel used an Experimental, Quantitative Approach
Advantages of pea plants for genetic study: There are many varieties with distinct heritable
features, or characters (such as color); character variations are called traits
Mating of plants can be controlled Each pea plant has sperm-producing organs
(stamens) and egg-producing organs (carpels) Cross-pollination (fertilization between different
plants) can be achieved by dusting one plant with pollen from another
1. Self-fertilization2. Cross-pollination
Mendel chose to track only those characters that varied in an “either-or” manner
He also used varieties that were “true-breeding” (plants that produce offspring of the same variety when they self-pollinate)
He spent 2 years getting “true” breeding plants to studyAt least three of his traits were available in seed catalogs of the
day
Mendel Planned Experiments Carefully
Mendel studied true breeding pea traits with two distinct forms
Terminology of BreedingP1 (parental) - pure breeding strain
F1 (filial) – offspring from a parental cross
They are also referred to as hybrids – because they are the offspring of two 2 pure-breeding parents
F2 - produced by self-fertilizing the F1 plants
LE 14-6Phenotype
Purple
Purple3
Purple
Genotype
PP(homozygous
Pp(heterozygous
Pp(heterozygous
pp(homozygous 1
2
1
Ratio 1:2:1
White
Ratio 3:1
1
Appearance:
P Generation
Genetic makeup:
Gametes
F1 Generation
Appearance:Genetic makeup:
Gametes:
F2 Generation
Purple flowersPp
P p1 21 2
P pF1 sperm
F1 eggs PP Pp
Pp pp
P
p
3 : 1
Purpleflowers
PP
Whiteflowers
pp
P p
The TestcrossHow can we tell the genotype of an individual
with the dominant phenotype?This individual must have one dominant allele,
but could be either homozygous dominant or heterozygous
The answer is to carry out a testcross: breeding the mystery individual with a homozygous recessive individual
If any offspring display the recessive phenotype, the mystery parent must be heterozygous
LE 14-7
Dominant phenotype,unknown genotype:
PP or Pp?
If PP,then all offspring
purple:
p p
P
P
Pp Pp
Pp Pp
If Pp,then 1
2 offspring purpleand 1
2 offspring white:
p p
P
Ppp pp
Pp Pp
Recessive phenotype,known genotype:
pp
Mendel’s Second Law: The Law of Independent Assortment
Mendel derived the law of segregation by following a single character
The F1 offspring produced in this cross were all heterozygous for that one character
A cross between such heterozygotes is called a monohybrid cross
Mendel identified his second law of inheritance by following two characters at the same time
Crossing two, true-breeding parents differing in two characters produces dihybrids in the F1 generation, heterozygous for both characters
A dihybrid cross, a cross between F1 dihybrids, can determine whether two characters are transmitted to offspring as a package or independently
LE 14-8
P Generation
F1 Generation
YYRR
Gametes YR yr
yyrr
YyRrHypothesis ofdependentassortment
Hypothesis of independent assortment
SpermEggs
YR
Yr
yrYR
YR
yr
Eggs
YYRR YyRr
YyRr yyrr yR
yrPhenotypic ratio 3:1
F2 Generation(predictedoffspring)
YYRR YYRr YyRR YyRr
YYRr YYrr YyRr Yyrr
YyRR YyRr yyRR yyRr
YyRr Yyrr yyRr yyrr
Phenotypic ratio 9:3:3:1
YR Yr yR yr
Sperm
1 21 4
1 4
1 4
1 4
1 43 4
1 2
1 2
1 2
1 4
9 16 3 16 3 16 3 16
1 4 1 4 1 4
The law of independent assortment states that each pair of alleles segregates independently of other pairs of alleles during gamete formation
Strictly speaking, this law applies only to genes on different, nonhomologous chromosomes
Genes located near each other on the same chromosome tend to be inherited together
ProbabilityRanges from 0 to 1Probabilities of all possible events must add up
to 1Rule of multiplication: The probability that
independent events will occur simultaneously is the product of their individual probabilities.
Rule of addition: The probability of an event that can occur in two or more independent ways is the sum of the different ways.
Multiplication and Addition Rules Applied to Monohybrid Crosses
The multiplication rule states that the probability that two or more independent events will occur together is the product of their individual probabilities
Probability in an F1 monohybrid cross can be determined using the multiplication rule
Segregation in a heterozygous plant is like flipping a coin: Each gamete has a 1/2 chance of carrying the dominant allele and a 1/2 chance of carrying the recessive allele
½ chance of P and ½ chance of p allele results in ¼ chance of each homozygous genotype.
There are two ways to get the heterozygous genotype so it is ¼ + ¼ = ½ Three genotypes give the same phenotype.
Solving Complex Genetics Problems with the Rules of Probability
We can apply the rules of multiplication and addition to predict the outcome of crosses involving multiple characters
A dihybrid or other multicharacter cross is equivalent to two or more independent monohybrid crosses occurring simultaneously
In calculating the chances for various genotypes, each character is considered separately, and then the individual probabilities are multiplied together
YYRR yyrr
YyRr
Male gametes
Female Gametes
YyRr
YyRr
¼
¼
¼
¼
¼ ¼ ¼ ¼ YR Yr yR yr
YR
Yr
yR
yr
YYRR YYRr
YYrR YYrr
YyRR YyRr
YyRr Yyrr
YyRR YyRr
YyRr Yyrr yyRr
yyRr
yyrr
yyRR9/16
3/16
3/16
1/16
For a dihybrid cross – the chance that 2 independent events occur together is the product of their chances of occurring separately.
The chance of yellow (YY or Yy) seeds= 3/4 (the dominant trait)
The chance of round (RR or Rr) seeds = 3/4 (the dominant trait)
The chance of green (yy) seeds= 1/4 (the recessive trait) The chance of wrinkled (rr) seeds= 1/4 (the recessive trait) Therefore:The chance of yellow and round= 3/4 x 3/4 = 9/16The chance of yellow and wrinkled= 3/4 x 1/4 = 3/16The chance of green and round= 1/4 x 3/4 = 3/16The chance of green and wrinkled= 1/4 x 1/4 = 1/16
Inheritance patterns are often more complex than predicted by Mendel
The relationship between genotype and phenotype is rarely as simple as in the pea plant characters Mendel studied
Many heritable characters are not determined by only one gene with two alleles
However, the basic principles of segregation and independent assortment apply even to more complex patterns of inheritance
Extending Mendelian Genetics for a Single Gene
Inheritance of characters by a single gene may deviate from simple Mendelian patterns in the following situations: When alleles are not completely dominant or
recessive When a gene produces multiple phenotypes When a gene has more than two alleles The forensic characteristics usually have more
than two alleles
The Spectrum of Dominance Complete dominance occurs when phenotypes of
the heterozygote and dominant homozygote are identical
In incomplete dominance, the phenotype of F1 hybrids is somewhere between the phenotypes of the two parental varieties
In codominance, two dominant alleles affect the phenotype in separate, distinguishable ways
Forensic Traits are codominant
RedCRCR
Gametes
P Generation
CR CW
WhiteCWCW
PinkCRCW
CRGametes CW
F1 Generation
F2 Generation EggsCR CW
CR
CRCR CRCW
CRCW CWCWCW
Sperm
12
12
12
12
12
12
The Relation Between Dominance and Phenotype
A dominant allele does not subdue a recessive allele; alleles don’t interact
Alleles are simply variations in a gene’s nucleotide sequence
For any gene, dominance/recessiveness relationships of alleles depend on the level at which we examine the phenotype
If you look directly at DNA, you can always detect codominance.
Frequency of Dominant Alleles
Dominant alleles are not always more common in populations than recessive alleles
For example, one baby out of 400 in the USA is born with extra fingers or toes
The allele for this trait is dominant to the allele for the more common trait of five digits per appendage
In this example, the recessive allele is far more prevalent than the dominant allele in the population
Multiple AllelesMost genes exist in populations in more
than two allelic formsFor example, the four phenotypes of the
ABO blood group in humans are determined by three alleles for the enzyme (I) that attaches A or B carbohydrates to red blood cells: IA, IB, and i.
Polygenic Inheritance• Quantitative characters are those that vary
in the population along a continuum• Quantitative variation usually indicates
polygenic inheritance, an additive effect of two or more genes on a single phenotype
• Skin color in humans is an example of polygenic inheritance
LE 14-12
aabbcc Aabbcc AaBbcc AaBbCc AABbCc AABBCc AABBCC
AaBbCcAaBbCc
20/64
15/64
6/64
1/64
Frac
tion
of p
roge
ny
Nature and Nurture: The Environmental Impact on Phenotype
Relating Mendel’s Laws to Cells• Law of Segregation• Pairs of
characteristics (alleles) separate during gamete formation
• Each cell has two sets of chromosomes that are divided to one set per gamete.
Law of Independent Assortment
The inheritance of an allele of one gene does not influence the allele inherited at a second gene.
Genes on different chromosomes segregate their alleles independently.
Offspring acquire genes from parents by inheriting chromosomes
Children do not inherit particular physical traits from their parents
It is genes that are actually inheritedGenes are carried on chromosomes.Mendel identified 7 sets of characters- One per
each of the 7 chromosomes in peas, so his law worked out perfectly.
Two characters on the same chromosome are linked together and would have messed up his law.
Inheritance of GenesGenes are the units of heredityGenes are segments of DNAEach gene has a specific locus on a
certain chromosomeOne set of chromosomes is inherited
from each parentReproductive cells called gametes
(sperm and eggs) unite, passing genes to the next generation
Sexual ReproductionTwo parents give rise to offspring that have
unique combinations of genes inherited from the two parents.
All humans arise from the joining of 1 egg and 1 sperm cell
100% of a person’s DNA is the same within and throughout a human being’s body.
Whether you look at the cells of a person’s blood, skin, semen, saliva or hair, the DNA and genes will be the same.
Chromosomes Come in Sets
• Each human cell (except gametes) has 46 chromosomes arranged in pairs in its nucleus
The two chromosomes in each pair are called homologous chromosomes
One of each pair came from your mother and the other came from your father.
Both chromosomes in a pair carry genes controlling the same inherited characteristics
The sex chromosomes are called X and YHuman females have a homologous pair
of X chromosomes (XX)Human males have one X and one Y
chromosomeThe 22 pairs of chromosomes that do not
determine sex are called autosomes
Each pair of homologous chromosomes includes one chromosome from each parent
The 46 chromosomes in a human somatic cell are two sets of 23: one from the mother and one from the father
The number of chromosomes in a single set is represented by n
A cell with two sets is called diploid (2n)For humans, the diploid number is 46 (2n = 46)
Meiosis reduces of chromosome number from diploid to haploid
The behavior of chromosomes during meiosis and fertilization is responsible for most of the variation that arises in each generation
Meiosis is preceded by the replication of chromosomes
Meiosis takes place in two sets of cell divisions, called meiosis I and meiosis II
The two cell divisions result in four daughter cells
Each daughter cell has only half as many chromosomes as the parent cell
Key
Maternal set ofchromosomes
Paternal set ofchromosomes
Possibility 1 Possibility 2
Combination 2Combination 1 Combination 3 Combination 4
Daughtercells
Metaphase II
Two equally probablearrangements ofchromosomes at
metaphase I
vvvvvvvvvvvvvvvvvvvvvvvvvvvvvvv
Maternal set ofchromosomes (n = 3)
2n = 6Paternal set ofchromosomes (n = 3)
Two sister chromatidsof one replicatedchromosomes
Two nonsister chromatids in a homologous pair
Pair of homologouschromosomes(one from each set)
Centromere
8 Gamete Combinations
LE 13-5
Key
Haploid (n)Diploid (2n)
Haploid gametes (n = 23)
Ovum (n)
Spermcell (n)
TestisOvary
Mitosis anddevelopment
Multicellular diploidadults (2n = 46)
FERTILIZATIONMEIOSIS
Diploidzygote(2n = 46)
Homologous pairs of chromosomes orient randomly at metaphase I of meiosis
In independent assortment, each pair of chromosomes sorts maternal and paternal homologues into daughter cells independently of the other pairs
The number of combinations possible when chromosomes assort independently into gametes is 2n, where n is the haploid number
For humans (n = 23), there are more than 8 million (223) possible combinations of chromosomes
Random Fertilization
Random fertilization adds to genetic variation because any sperm can fuse with any ovum (unfertilized egg)
The fusion of gametes produces a zygote with any of about 64 trillion diploid combinations
Crossing over adds even more variationEach zygote has a unique genetic identity
LE 13-11Prophase Iof meiosis
Tetrad
Nonsisterchromatids
Chiasma,site of crossingover
Recombinantchromosomes
Metaphase I
Metaphase II
Daughtercells
Monohybrid Cross: - cross involving only one character.
Results from CrossesF1 offspring -
the trait expressed was the same as that of one of the parental lines
traits did not blendF2 offspring
the traits from both parents were expressed in a 3:1 ratio
while the trait had not been expressed in the F1, it remained unchanged as it was passed from the P1 to the F1 and then to the F2 generation.
CONCLUSIONTraits are inherited as discrete, separate
units.
Mendel’s Conclusions
1. Factors (genes) that determine traits can be hidden or unexpressed.
Dominant traits have a factor (gene) that is expressed in the F1 offspring
Recessive traits have a factor (gene) that is not expressed in the F1 offspring
Mendel’s Conclusions
2. Despite P1 and F1 generations appearing identical, they must be genetically different.
Phenotype- observed properties of a trait
Genotype- the genetic makeup of a trait
PP1 and F1 seeds have the same phenotype but different genotypes
3. Since the F1 offspring had factors (genes) for both smooth and wrinkled - then there must be at least 2 factors for every trait.
• Alleles- alternative forms of a gene• Genotype- indicates the combination of alleles
present • Phenotype- indicates the trait observed
These terms differentiate the observed form and the underlying alleles present at a particular gene.
Mendel’s Conclusions
Mendel’s Model
Mendel developed a hypothesis to explain the 3:1 inheritance pattern he observed in F2 offspring
Four related concepts make up this modelThese concepts can be related to what we
now know about genes and chromosomes
Alternative versions of genes account for variations in inherited characters
For example, the gene for flower color in pea plants exists in two versions, one for purple flowers and the other for white flowers
These alternative versions of a gene are now called alleles
Each gene resides at a specific locus on a specific chromosome
The First Concept
Allele for purple color
Homologouspair ofchromosomes
Allele for white color
Locus for flower color gene
For each character, an organism inherits two alleles, one from each parent
Mendel made this deduction without knowing about the role of chromosomes
The two alleles at a locus on a chromosome may be identical, as in the true-breeding plants of Mendel’s P generation
Alternatively, the two alleles at a locus may differ, as in the F1 hybrids
The Second Concept
The Third Concept
If the two alleles at a locus differ, then one (the dominant allele) determines the organism’s appearance, and the other (the recessive allele) has no noticeable effect on appearance
In the flower-color example, the F1 plants had purple flowers because the allele for that trait is dominant
The Fourth ConceptKnown as “the law of segregation”Two alleles for a heritable character separate
(segregate) during gamete formation and end up in different gametes
Thus, an egg or a sperm gets only one of the two alleles that are present in the somatic cells of an organism
This segregation of alleles corresponds to the distribution of homologous chromosomes to different gametes in meiosis
Mendel’s Laws Explain his DataMendel’s segregation model accounts for the 3:1
ratio he observed in the F2 generation of his numerous crosses
The possible combinations of sperm and egg can be shown using a Punnett square, a diagram for predicting the results of a genetic cross between individuals of known genetic makeup
A capital letter represents a dominant allele, and a lowercase letter represents a recessive allele
It is the basis for Mendel’s Law of Segregation
Pairs of characteristics separate during gamete formation.
What does the 3:1 ratio of dominant to recessive traits in the F2 population mean?
Review of meiosis
Monohybrid Cross: - cross involving only one character.
Two types of “states”
Homozygous: an individual or a locus carries identical
alleles of a given gene.
Heterozygous: an individual or a locus carries different
alleles of a given gene
Gametes join randomly to make new individuals
Reginald C. PunnettThe Punnett Square
Mendel’s Law of Segregation
Members of a gene pairs (alleles) separate from each other during gamete formation.
The underlying mechanism is separation and then segregation of homologous chromosomes during meiosis.
Key terms: dominant and recessive traits genotype versus phenotype
Mendel’s Law of Segregation holds true for any cross
Molecular Basis of Mendel’s factors
Mendel’s factors are called alleles. versions of the same gene or DNA
sequence. differ in DNA sequence at one or more sites.
Phenotype Genotype Abbreviation of Genotype
Tall plant Homozygous dominant “tall associated” alleles.
TT
Tall Plant Heterozygous Tt
Short Plant Homozygous dominant “short associated” alleles.
tt
Genotype and Phenotype
Dihybrid CrossesParental lines:
smooth yellow seed wrinkled green seeds
Mendel learned from previous monohybrid crosses smooth was dominant over wrinkled yellow was dominant over green
Pure-breeding smooth yellow genotype SSYY Pure-breeding green wrinkled genotype ssyy
Dihybrid Cross
?
315 smooth and yellow parental108 smooth and green new combo101 wrinkled and yellow new combo32 wrinkled and green parental
9:3:3:1
Dihybrid cross - F2 generation
Fig 3.8
Dihybrid Cross
Total smooth 315 + 108 = 423Total wrinkled 101 +32 = 133 ~ 3:1 Total yellow 315 + 101 = 416Total green 108 + 32 = 140 ~ 3:1
Each trait is behaving as expected for a monohybrid cross.
Inheritance of each trait appears to be independent of the other trait.
How does this dihybrid F2 phenotypic ratio of 9:3:3:1 relate to the monohybrid cross
phenotypic ratio of 3:1?
Mendel’s Conclusion
He reasoned that alleles from one gene pair segregate into gametes independently of the alleles belonging to other traits, producing gametes with all possible combinations of alleles.
Law of Independent Assortment
The inheritance of an allele of one gene does not influence which allele is inherited at a second gene.
Two genes on different chromosomes segregate their alleles independently.
Law of independent assortment
Probability: The likelihood that an event will occur
•No chance of event probability = 0(e.g. chance of rolling 8 on a six-sided die)
•Event always occurs probability = 1 (chance of rolling 1,2,3,4,5,or 6 on a six-sided die)
# on die probability
1 1/6
2 1/6
3 1/6
4 1/6
5 1/6
6 1/6
The probability of an event
= # of chance of event total possible events
The probabilities of all the possible events add up to 1.
Independent Events• The probability of independent events is
calculated by multiplying the probability of each event.
In two rolls of a die, the chance of rolling the number 3 twice:
Probability of rolling 3 with the first die = 1/6
Probability of rolling 3 with the second die = 1/6
Probability of rolling 3 twice = 1/6 x 1/6 or 1/36
Independent events
What is the chance of an offspring having the homozygous recessive genotype when both parents are doubly heterozygous?
Independent Events
Dependent EventsThe probability of dependent events is calculated
by adding the probability of each event.
In one roll of a die, what is the probability of rolling either the number 5 or an even number?
Probability of rolling 5 or an even number = 1/6 + 3/6 or 4/6
Probability of rolling the number 5 = 1/6
Probability of rolling an even number = 3/6
Parents are heterozygous for a trait, R.
What is the chance that their child carries at least one dominant R allele?
Probability of child carrying RR = 1/4Probability of child carrying Rr = 1/2
Probability of child carrying R = 1/4 + 1/2 = 3/4
Dependent Events
1/2
1/2
1/2 1/2
So, Rr genotype = (1/2 x 1/2) x 2 = 1/2 RR genotype is (1/2 x 1/2) = ¼Add these to get the combined probability.
R rR
r
RR
Rr
Rr
rr
Can use to solve more complicated problems:
AaBBccDdEeFFGghhIiJJKk x aaBbCCDdEEffggHhIIjjKk
Crossing Double Heterozygotes
Fig 3.10b
Fig 3.11
Dihybrid Cross
From the 16 possible fertilization events
- 9 genotypes - 4 phenotypes 9:3:3:1
Dihybrid cross
Tetrahybrid cross!
Statistical Analysis
Simple cross: purple x whiteF1: all purpleF2: 2850 purple, 1150 white
Use Χ2 test to determine likelihood of getting this result by chanceΧ2 = total of (observed-expected)2/expected over all classes"Expected" is from null hypothesis - data fit a 3:1 ratio(2850-3000)2/3000 + (1150-1000)2/1000 = 30!
10x as many, butsame ratio
P is <<less than 5%, so data are significantly different from null hypothesis
Pedigree Analysis
Inborn errors of metabolismHint: much more common in first cousin marriages
Garrod, 1902 - human traits followed Mendelian rules