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Human 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?

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Human Genetics

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  1. Human Genetics Mendelian Genetics

  2. 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?

  3. Darwin Prior to Mendel Scientists 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 hypothesis The “particulate” hypothesis: parents pass on discrete heritable units (genes) Mendel’s experiments suggested that inherited traits were discrete and constant

  4. http://www.mendel-museum.org/eng/1online/experiment.htm Why did Mendel succeed in seeing something that nobody else saw? He counted Chose a good system Chose true-breeding characters Gregor Mendel

  5. The field of genetics started with a single paper!

  6. 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.

  7. 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

  8. Self-fertilization Cross-pollination

  9. Mendel Planned Experiments Carefully • 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 study • At least three of his traits were available in seed catalogs of the day

  10. Mendel studied true breeding pea traits with two distinct forms

  11. Terminology of Breeding P1 (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

  12. Genotype Phenotype PP (homozygous Purple 1 LE 14-6 Pp (heterozygous 3 Purple 2 Pp (heterozygous Purple pp (homozygous White 1 1 Ratio 1:2:1 Ratio 3:1

  13. P Generation Purple flowers PP White flowers pp Appearance: Genetic makeup: p P Gametes F1 Generation Appearance: Genetic makeup: Purple flowers Pp Gametes: 1 1 p P 2 2 F1 sperm P p F2 Generation P PP Pp F1 eggs p Pp pp 3 : 1

  14. The Testcross • How 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 themystery individual with a homozygous recessive individual • If any offspring display the recessive phenotype, the mystery parent must be heterozygous

  15. 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 model • These concepts can be related to what we now know about genes and chromosomes

  16. The First Concept • 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

  17. Allele for purple color Homologous pair of chromosomes Locus for flower color gene Allele for white color

  18. The Second Concept • 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

  19. 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

  20. The Fourth Concept • Known 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

  21. Mendel’s Laws Explain his Data • Mendel’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

  22. 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

  23. 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

  24. Garrod, 1902 - human traits followed Mendelian rules Inborn errors of metabolism Hint: much more common in first cousin marriages

  25. Dominant phenotype, unknown genotype: PP or Pp? Recessive phenotype, known genotype: pp LE 14-7 If Pp, then 1 2 offspring purple and 1 2 offspring white: If PP, then all offspring purple: p p p p P P Pp Pp Pp Pp P P pp pp Pp Pp

  26. 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

  27. 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

  28. P Generation YYRR yyrr Gametes yr YR YyRr F1 Generation Hypothesis of dependent assortment Hypothesis of independent assortment LE 14-8 Sperm YR Yr yR yr 1 1 1 1 4 4 4 4 Sperm Eggs YR yr 1 1 2 2 YR 1 4 Eggs YYRR YYRr YyRR YyRr YR 1 2 F2 Generation (predicted offspring) YYRR YyRr Yr 1 4 YYRr YYrr YyRr Yyrr yr 1 2 YyRr yyrr yR 1 4 YyRR YyRr yyRR yyRr 3 1 4 4 yr 1 4 Phenotypic ratio 3:1 YyRr Yyrr yyRr yyrr 9 3 3 3 16 16 16 16 Phenotypic ratio 9:3:3:1

  29. 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

  30. Probability • Ranges from 0 to 1 • Probabilities of all possible events must add up to 1 • Rule 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.

  31. Probability: The likelihood that an event will occur The probability of an event = # of chance of event total possible events • 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) The probabilities of all the possible events add up to 1.

  32. 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

  33. Independent events What is the chance of an offspring having the homozygous recessive genotype when both parents are doubly heterozygous?

  34. Independent Events

  35. Dependent Events The 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 the number 5 = 1/6 Probability of rolling an even number = 3/6 Probability of rolling 5 or an even number = 1/6 + 3/6 or 4/6

  36. Parents are heterozygous for a trait, R. What is the chance that their child carries at least one dominant R allele? Dependent Events Probability of child carrying RR = 1/4 Probability of child carrying Rr = 1/2 Probability of child carrying R = 1/4 + 1/2 = 3/4

  37. 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

  38. 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.

  39. 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

  40. YYRR yyrr Female Gametes YyRr ¼ ¼ ¼ ¼ YyRr YR Yr yR yr ¼ ¼ ¼ ¼ YR Yr yR yr YYRR YYRr YyRR YyRr YyRr Male gametes YYrR YYrr YyRr Yyrr 9/16 YyRR YyRr yyRR yyRr 3/16 3/16 YyRr Yyrr yyRr yyrr 1/16

  41. 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 = 9/16 The chance of yellow and wrinkled= 3/4 x 1/4 = 3/16 The chance of green and round= 1/4 x 3/4 = 3/16 The chance of green and wrinkled= 1/4 x 1/4 = 1/16

  42. RR Rr Rr rr 1/2 1/2 r R 1/2 R r 1/2 So, Rr genotype = (1/2 x 1/2) x 2 = 1/2 RR genotype is (1/2 x 1/2) = ¼ Add these to get the combined probability. Can use to solve more complicated problems: AaBBccDdEeFFGghhIiJJKk x aaBbCCDdEEffggHhIIjjKk

  43. Crossing Double Heterozygotes

  44. Fig 3.10b

  45. Fig 3.11

  46. Dihybrid Cross From the 16 possible fertilization events - 9 genotypes - 4 phenotypes 9:3:3:1

  47. Tetrahybrid cross! Dihybrid cross

  48. 10x as many, but same ratio Statistical Analysis Simple cross: purple x white F1: all purple F2: 2850 purple, 1150 white Use Χ2 test to determine likelihood of getting this result by chance Χ2= 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! P is <<less than 5%, so data are significantly different from null hypothesis

  49. 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

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