Transmission Genetics 2, material from Human Genetics, 7th edition by Ricki Lewis

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1 A. Outline: Transmission Genetics 2, material from Human Genetics, 7th edition by Ricki Lewis B. Reading assignment: Read Lewis Human Genetics Chapter 4, pages 85-88, 91 (summary of ). C. Suggested practice questions: Chapter 4 Review questions: 1, 2, 3a-d, 4, 5, 7, 8; Applied questions: 4, 5, 13 Recap: Mendel s First Law the Law of Segregation Mendel s monohybrid cross revealed how one trait is transmitted from generation to generation. Mendels interpretation - GENES ARE IN PAIRS!!! A 'thing' from the pollen and a 'thing' from the egg determine height in the offspring. Now we know that the 'thing' is a gene. An egg provides one copy of the height gene and the pollen provides the other copy of the height gene to the progeny plant. The progeny plant ends up with two height genes, one from each parent gamete. Mendel hypothesized that the paired genes of each parent separate when gametes are formed. Separation of the paired genes in the parent (also known as segregation) occurs during meiosis, the process that gives rise to haploid gametes (egg and pollen/sperm). This is the basis for the Law of Segregation. Mendel s First Law - The Law of Segregation Mendel hypothesized that during the formation of pollen and egg, the genes separate (or segregate) randomly. Heterozygous parents of the genotype Tt produce gametes with a T allele at the same frequency that they produce gametes that carry the t allele. Homozygous TT parents produce gametes that carry the T allele. Homozygous tt parents produce gametes that carry the t allele. The Law of Segregation is supported by the following observation: when hybrids self-fertilize (recall the self cross, Tt X Tt), the T and t alleles are sorted randomly and each appears in equal proportions. 1

2 When chromosomes were described, it was apparent that Mendel s ratios could be explained by the segregation of chromosomes. 1. Genes and chromosomes separate at each generation and each parent passes one copy to the offspring. 2. Genes and chromosomes are inherited in random combinations. Another important point, in the case of peas for the traits and genes that Mendel studied, the alleles do not blend. The T allele exhibits complete dominance over the t allele. TT and Tt specify a tall plant, whereas tt specifies a short plant. Mendel found the same to be true for all of the traits he studied. In each case, he found the trait to be controlled by a single gene with two different alleles, one dominant and one recessive. Mendel concluded that heredity or inheritance is controlled by genes that do not blend, but maintain their character from generation to generation. Mendel next wanted to determine if two different genes segregate independently of one another. He did these experiments by following two different traits through genetic crosses. The results of these experiments led to the development of Mendel s second law, the Law of Independent Assortment. Mendel started with two parents that were each true breeduing for two traits. In this example, one parent was tall with smooth peas and the other parent was short with wrinkled peas. First, he performed crosses to combine the alleles of the two true breeding peas tall smooth X short wrinkled. The P 1 genotypes are TTSS X ttss, this cross produced tall progeny with smooth peas with the genotype TtSs in the F 1 generation. Mendel knew that tall and smooth were the dominant phenotypes from his previous experiments. Now Mendel performed a self-cross with the TtSs progeny, this is called a dihybrid cross (dihybrid = two traits (di) each with 2 different alleles (hybrids)). The Punnet square for this cross is more complex because we are now following two traits. Using the Punnet square to determine the probability of each type of 2

3 offspring, we assume that segregation of T or t (and S or s) alleles into gametes is random. TS Ts ts ts TS TTSS TTSs TtSS TtSs Ts TTSs TTss TtSs Ttss ts TtSS TtSs ttss ttss ts TtSs Ttss ttss ttss From the dihybrid cross, Mendel found progeny phenotypes in the following ratios: 9 - Tall smooth 3 - Tall wrinkled 3 - Short and smooth 1 - Short and wrinkled What is the expected ratio of progeny genotypes from the dihybrid cross? The ratios of progeny genotypes and phenotypes indicate that the two traits are segregating independently. Mendel proposed a second Law of Inheritance based on the findings of the dihybrid cross he called this the Law of Independent Assortment. Meiosis is the basis for Mendel's Laws of Segregation and Independent Assortment. This is illustrated in Figures 4.4 and 4.9 of the Lewis Human Genetics textbook. Recap - dihybrid cross 1. Mendel crossed true breeding tall smooth to short wrinkled. 2. The F 1 progeny were tall and smooth. 3. To show that the genes for plant height and pea shape did not influence each other, he performed a dihybrid cross by selfing the F1 progeny, TtSs. 4. The ratios of progeny indicated that the traits segregate independently. 5. Test crosses were performed to determine genotype of the F 2 progeny expressing dominant phenotypes by crossing to ttss plants. From his dihybrid cross data, Mendel developed the Law of Independent Assortment that states that two genes on different chromosomes segregate their alleles independently. The inheritance of an allele of one gene on one chromosome 3

4 does not influence the inheritance of an allele of a second gene on a different chromosome. Crossing squares or Punnet squares: The number of squares needed is 4 n, where n is the number of traits being followed. 1 trait, n=1 so the number of boxes is 4 1 or 4 2 traits, n=2 so the number of boxes is 4 2 or 16 3 traits, n=3 so the number of boxes is 4 3 or 64 4 traits, n=4 so the number of boxes is 4 4 or 256 Bottom line - the crossing square can get to be too big if you want to follow large numbers of traits!!! I will show you some simple mathematical rules for estimating probabilities of offspring in the next lecture. Human Traits: Modes of inheritance: these are rules that explain common patterns that inherited disease traits follow as they pass through families. The pattern can reveal if a disease trait is dominant or recessive and if it is carried on an autosome or a sex chromosome. We will focus on autosomal inheritance, the inheritance of genes on the autosomes (after exam 1, we will study the patterns of inheritance of genes carried on the X and Y chromosomes, known as sex-linked traits). Autosomal dominant traits: - can occur in males and females - can be transmitted by male and female parent - do not skip generations, child that inherits a dominant allele is affected - if a child has a dominant disease or trait, then one parent must be afflicted - if none of the offspring inherit the dominant allele, then transmission stops In the following cross following the dominant disease Achondroplasia (dwarfism, short limbs, normal head and trunk), the Aa parent is affected and the aa parent is not affected. Based on Punnet s square, there is a 50% chance or probability that an offspring will inherit an A allele, and thereby be affected. 4

5 Other autosomal dominant conditions include Huntington disease, polycystic kidney disease and myotonic dystrophy. Autosomal recessive traits: - can occur in both sexes - affected individual is homozygous recessive - heterozygous individuals are called carriers because the wild-type allele masks the mutant allele. Usually heterozygotes are unaffected (do not exhibit the disease). - trait can skip generations - just like shortness in pea plants - parents of an affected offspring are either carriers or exhibit the trait. Some examples of autosomal recessive diseases are Cystic fibrosis, Sickle-cell anemia and Tay-Sachs disease. In the following cross, both parents are carriers of the recessive c allele for cystic fibrosis If both parents are carriers of the c allele, then based on the Punnet s square, the probability that a progeny will inherit c c is 1/4 or 25%. If only one parent is a carrier, then there is a 0% probability of inheriting the disease, but a 50% probability of inheriting one copy of c and being a carrier. Question: If two carriers who have one child, who inherited cc, have a second child, what is the probability that the second child will inherit cc? Answer: Each offspring is a new event and the genes it will inherit are not affected by the genotypes of previous children. Set up a Punnet s square for the cross Cc X Cc. Determine the chance or probability of a c c offspring. (25%) 5

6 Question: Based on a Cc X Cc cross, what is the probability that an offspring will not inherit the disease? Answer: The probability of a CC offspring = 1/4 and the probability of Cc = 1/2. Therefore, 1/4 +1/2 = 3/4, which is the same as 1 minus 1/4 (the probability of inheriting c c ). Human traits governed by a single gene. Can you follow the pattern of inheritance for any of these traits in your family? Curly hair is dominant over straight hair: CC and Cc individuals have curly hair, c c individuals have straight hair A Widow s peak is dominant over a straight hariline. A cleft chin is dominant over a round chin. Having body hair is dominant over being hairless. Freckles are dominant over non-freckled skin. Bent pinky finger (bends toward ring finger) is dominant over straight pinky. The ability to roll the tongue is dominant. Free or detached ear lobes are dominant to attached ear lobes. The ability to bend the thumb backward to nearly a 90 degree angle is a recessive trait (hh). HH or Hh individuals (with the dominant allele) can bend the thumb back about 30 degrees. 6

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