Genetics Part II: Probability and Pedigree Nestor T. Hilvano, M.D., M.P.H. (Images Copyright Discover Biology, 5th ed., Singh-Cundy and Cain, Textbook, 2012.)

Learning Objectives Explain the rule of multiplication and the rule of addition to determine the probability of an event in monohybrid crosses. Explain how family pedigrees can help determine the inheritance of human traits. Discuss and provide examples of how recessive and dominant disorders are inherited. Describe the inheritance patterns of pleiotropy and polygenic inheritance.

Laws of Probability Govern Mendelian Inheritance The probability of a specific event is the number of ways that event can occur out of the total possible outcomes. # of actual occurrences Probability = ______________________ # of possible occurrence When tossing a coin, the outcome of one toss has no impact on the outcome of the next toss In the same way, the alleles of one gene segregate into gametes independently of another gene’s alleles Ex: flipping heads on a coin= ½ (50%)

Rules of Probability Independent events – ex. Tossing of coin Rule of Multiplication – probability of 2 events occuring together is the product of the probabilities of the 2 events occuring apart Ex. Probability of recessive phenotype occuring in monohybrid? ½ x ½ = ¼ dihybrid? ¼ x ¼ = 1/16

Rule of Addition – probabilities are added if there is more than one way an outcome can occur, as in determining the chances for F2 heterozygous offspring Ex. Probability of Bb is ¼ + ¼ = ½

Degrees of Dominance Complete dominance occurs when phenotypes of the heterozygote and dominant homozygote are identical Incomplete dominance, the phenotype of F1 hybrids is somewhere between the phenotypes of the two parental varieties Codominance, two dominant alleles affect the phenotype in separate, distinguishable ways; Type AB blood is an example

Incomplete dominance In snapdragon Fig. 14-10-3 P Generation Red White CRCR CWCW Gametes CR CW Incomplete dominance In snapdragon Pink F1 Generation CRCW Gametes 1/2 CR 1/2 CW Figure 14.10 Incomplete dominance in snapdragon color Sperm 1/2 CR 1/2 CW F2 Generation What is the Phenotype ratio? _____________ 1/2 CR CRCR CRCW Eggs 1/2 CW CRCW CWCW

Figure 12.11 Genetic Basis of the ABO Blood Types in Humans The ABO blood types are determined by chains of sugars covalently attached to certain cell surface proteins on red blood cells. Type A red blood cells have a distinctive “A type” of sugar (chemically, N-acetylgalactosamine), whereas type B blood cells have a “B type” of sugar (galactose) at the end of the chain. The AB blood type reflects codominance: the red blood cells in type AB blood have about equal amounts of A-type sugars and B-type sugars on their cell surface. The I gene encodes an enzyme that comes in at least two allelic forms: the form encoded by the A allele adds A-type sugars to red blood cell surfaces, and the form encoded by the B allele adds B-type sugars. The i allele codes for a nonfunctional version of the enzyme that cannot attach any sugar to the cell surface protein. People who have two copies of the i allele (homozygotes) are said to have blood type O.

Pedigree Analysis Figure 9.8A Dominant Traits Recessive Traits Pedigree is a family tree that describes the interrelationships of parents and children Inheritance patterns of particular traits can be traced and described can be used to make predictions of future offspring Dominant-recessive inheritance Apply Mendelian laws Freckles No freckles Widow’s peak Straight hairline Figure 9.8A Examples of single-gene inherited traits in humans Free earlobe Attached earlobe 9

Brachydactyly: dominant condition marked by short/clubbed fingers & toes Figure 13.9 (Part 2) Patterns of Inheritance Can Be Analyzed in Family Pedigrees The pedigree shown here illustrates symbols commonly used by geneticists. The Roman numerals at left identify different generations. Numbers listed below the symbols identify individuals of a given generation. This pedigree charts the inheritance of brachydactyly, a dominant condition marked by short or clubbed fingers and toes. Brachydactyly was the first genetic condition to be analyzed, in 1903, by following pedigrees.

Recessive Disorders Most common; affected children are homozygous recessive Born to normal parents who are both heterozygotes (Dd) Ex. Deafness, albinism, cystic fibrosis, PKU, sickle-cell disease, etc. Practice: construct punnett squares Parents – both Dd (normal but are carriers) Gametes: D and d Probability for Hearing (DD, Dd)= ¾ (75%); Deaf (dd)= ¼ (25%); Carriers (Dd)= 2/4 (50%)

Dominant Disorders Homozygous dominant causes death of embryo; only heterozygous have this disorder ; 50% chance of passing the condition Ex. Achondroplasia (dwarf), extrafingers or web digits, Huntington’s disease, and Hypercholesterolemia

Achondroplasia: a dominant trait disorder Fig. 14-17 Achondroplasia: a dominant trait disorder Parents Dwarf Normal Dd  dd Sperm D d Eggs Dd dd Figure 14.17 Achondroplasia: a dominant trait d Dwarf Normal Dd dd d Dwarf Normal

Pleiotrophy and Polygenic Inheritance Pleiotrophy = single gene produce multiple phenotypic characteristics. ex: sickle cell disease (ss) – confers phenotypic traits as anemia, weakness, mental dysfunction, organ damage, etc. Polygenic = 2 or more genes produce a single phenotypic characteristic. ex: mixtures of 3 genes (each w/ 2 alleles) for phenotype of skin color

Crossing Over can separate linked alleles Producing gametes with recombinant chromosomes (crossing over of linked genes) A B a b Tetrad Crossing over Gametes

Sex-linked Disorders in Humans Sex-linked genes determine the sex of individual and other inheritable characteristics Sex-linked disorders are due to recessive alleles For a recessive sex-linked trait to be expressed A female needs two copies of the allele A male needs only one copy of the allele Sex-linked recessive disorders are much more common in males than in females ex. Hemophilia (lack protein for blood clotting), Color blindness (red-green), Duchenne muscular dystrophy

Homework Define terms: recessive disorders; dominant disorders; polygenic inheritance; pleiotrophy; pedigree; recombinant chromosomes, and sex-linked genes. Describe the rule of multiplication and rule of addition in determining the probability of inheritance. Male with black hair (Bb) married a female with red hair (bb). Construct a punnett square to show the location of gametes and offspring. What is the probability of having a black hair? Probability of red hair? Whys is color blindness is more common in males?