Chapter 18. Genes and Medical Genetics

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1 1 Chapter 18 Genes and Medical Genetics 2 1

2 Outline Genotype vs. Phenotype Dominant vs. Recessive Traits Punnett Squares Autosomal Recessive Disorders Autosomal Dominant Disorders Pedigree Charts Multiple Allelic Traits Incomplete Dominance Sex-Linked Traits 3 Organization of human DNA 46 individual strands called chromosomes almost every cell contains 46 chromosomes stored in the nucleus - all the information to clone yourself 46 chromosomes arranged as 23 pairs: each has a partner strand inherited from the mother and father. Half of you is your mom, the other half is your dad. all genes on each paired set encode comparable products except for the sex chromosome pair: XX (female) and XY (male). each member of the pair can encode different versions of the same gene called alleles alleles arise from an original gene through evolutionary mutation This sexual reproduction stuff is complex 4 2

3 Shuffling the genetic deck: making gametes for growth and repair, cells need to multiply mitosis makes progeny cells with full DNA complement full DNA content (2n) is diploid for production of reproductive cells, gametes are formed gametes: eggs or sperm contain half the original DNA of parent meiosis: cell division process leading to gemete formation half DNA content (n) is haploid only one member of each chromosome pair is used to make the haploid gametes recombination occurs during meiosis to shuffle the alleles between members of each chromosome pair recombination allows mixture of alleles from father and mother to be passed on in gametes and increases genetic variability This sexual reproduction stuff is complex 5 Variability : the result of sexual reproduction haploid gametes combine at conception to restore the diploid chromosome content all mitochondrial DNA is inherited from the mother, not father alleles are mixed in meiosis, so each combination in the new individual will be unique combinations of genes determines everything from appearance, physical strengths and weaknesses, even behavior, intellegence,, emotional state sexual reproduction creates variety, a opposed to asexual reproduction occurring through cloning of DNA information but Dr. Sussman makes this seem easy 6 3

4 Genetics: understanding how genes combine to create the characteristics of an organism organisms inherit characteristics discretely through genes Charles Darwin thought inheritance was a matter of blending phenotypic characteristics (didn t t know about genes) blending would be bad news for natural selection, since any advantageous evolutionary trait would be diluted out through subsequent generations Gregor Mendel sorted it out and invented the science of genetics by studying inheritance in the 1930s. combination of natural selection and Medelian genetics is referred to as new synthesis Mendel had no idea of DNA, but observed specific phenotypes were passed on in his pea plants in a lawful manner 7 Genetics: it works like this alleles are often not equally weighted with regard to producing a given phenotype there are dominant and recessive alleles (e.g. tall versus short) if tall is dominant (T) over short (t), the phenotype of an individual with TT will be tall (both dominant alleles) the phenotype of an individual with tt will be short (both recessive alleles both TT or tt are called homozygous - alleles are the same the phenotype of an individual with Tt will be tall because the dominant gene determines the phenotype mixed alleles like this are heterozygous in real life, genetics are usually more complicated because many different genes combine together, alleles are not dominant over each other, influenced by gender, influenced by environment, or several alleles in the gene pool collectively form a hierarchy of dominance 8 4

5 Genotype and Phenotype Genotype refers to an individual s genes. Alleles are alternate forms of a gene. vdominant alleles are assigned uppercase letters, while recessive alleles are assigned lowercase letters. Homozygous Dominant = EE. Homozygous Recessive = ee. Heterozygous = Ee. Phenotype refers to an individual s physical appearance. 9 Genotype determines phenotype 10 5

6 Dominant/Recessive Traits Forming the Genes. Reduction of chromosome number occurs when pairs of chromosomes separate as meiosis occurs. 11 Gametogenesis - splitting up the genes Gametes have only one allele for each trait 12 6

7 Figuring the Odds A Punnett square is used to determine the phenotypic ratio among the offspring when all possible sperm are given an equal chance to fertilize all possible eggs. If both parents are heterozygous, each child has a 25% chance of exhibiting the recessive phenotype. 13 Inherited characteristics - a few examples 14 7

8 Heterozygous by heterozygous cross Punnett square - used to determine phenotypic ratio 15 Hetero by homozygous recessive cross 16 8

9 Dihybrid cross children of original pairing are heterozygous for two traits A 4x4 array yields 16 assortment possibilities in a ration of 9:3:3:1 Imagine the possible variations in the actual human population - limitless combinations 17 Autosomal Dominant Disorders Dominant disorders are passed on by a parent who has, or will develop, the disorder. Neurofibromatosis. vallele located on chromosome 17. Huntington Disease. vallele located on chromosome

10 Autosomal Recessive Disorders Recessive disorders can by passed on by parents who are unaffected. Tay-Sachs Disease. vallele located on chromosome 15. Cystic Fibrosis. vallele located on chromosome 7. Phenylketonuria. vallele located on chromosome Autosomal recessive disorders cause disease Cystic fibrosis - channel protein mutation leads to altered Cl ion transport Phenylketonuria - lack enzyme to metabolize phenylalanine Tay-Sachs - lack of enzyme hexosaminidase A leads to abnormal storage of glycosphingolipid in lysosomes Albanism - mutation of pigment gene melanin leading to lack of coloration Epistasis: : one gene affects expression of others (e.g. albinos also exhibit loss of pigment, so any genes responsible for coloration are not expressed 20 10

11 Twin traits: concordance suggests hereditary 21 Beyond Simple Inheritance Polygenic Inheritance. One trait is governed by two or more sets of alleles. vcontinuous variation of phenotypes. Skin Color

12 Polygenic inheritance - multiple alleles 23 Beyond Simple Inheritance Multiple Allelic Traits. Gene exists in several allelic forms, although an individual usually only has two of the possible alleles. vabo Blood Types. A - A antigen on red blood cells. B - B antigen on red blood cells. O - Neither A or B antigen on red blood cells

13 Inheritance of blood type: multiple alleles 25 Beyond Simple Inheritance Incomplete Dominance. Codominance occurs when alleles are equally expressed in a heterozygote. Incomplete Dominance is exhibited when the heterozygote has an intermediate phenotype between that of either heterozygote. vsickle Cell Disease. Heterozygotes protected from malaria

14 Incomplete dominance: intermediate phenotype 27 Sex-Linked Traits Traits controlled by alleles on the sex chromosomes are said to be sex-linked. X chromosome = X-linked. Y chromosome = Y-linked. Most sex-linked alleles are on the X chromosome. Red-Green Color Blindness. Muscular Dystrophy. Hemophilia

15 Barr bodies: inactivated X chromosome keeps sex-linked dosage constant recessive mutations appear in females as mosaics 29 Sex linked trait - color blindness Color blind females are more rare than males - need 2 recessive alleles 30 Color blind females are more rare than males - need 2 recessive alleles 15

16 X-linked disorders cause disease Color blindness: : lacking appropriate pigment in cone cells of retina Muscular dystrophy: abnormal dystrophin gene Hemophilia: : lack clotting factor VIII (A-type) or IX (B-type) 31 Sex-influenced traits - hormonal effects Testosterone causes effect 32 16

17 Review Genotype vs. Phenotype Dominant vs. Recessive Traits Punnett Squares Autosomal Recessive Disorders Autosomal Dominant Disorders Pedigree Charts Multiple Allelic Traits Incomplete Dominance Sex-Linked Traits 33 Remember: a given mutation in a gene that produces a beneficial consequence for the organisms capacity to reproduce can be spread as a distinct advantage to subsequent generations and will not be diltued out genes are inherited as distinct entities This sexual reproduction stuff is complex, but Dr. Sussman makes it seem easy 34 17

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