Human Genetics Concepts and Applications Fourteenth Edition PDF

Because learning changes everything.® Chapter 04 Single-Gene Inheritance HUMAN GENETICS Concepts and Applications Fourteenth Edition Ricki Lewis © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  Lea...

Because learning changes everything.® Chapter 04 Single-Gene Inheritance HUMAN GENETICS Concepts and Applications Fourteenth Edition Ricki Lewis © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  Learning Outcomes 1 1. List the characteristics that distinguish single-gene diseases from other types of diseases. 2. Describe how Mendel deduced that recessive traits seem to disappear in hybrids. 3. Define and distinguish heterozygote and homozygote; dominant and recessive; phenotype and genotype. 4. Explain how the law of segregation reflects the events of meiosis. 5. Indicated how a Punnett square is used to track inheritance patterns. 6. Explain how a gene alone may not solely determine a trait. © McGraw Hill 2  Learning Outcomes 2 1. Distinguish between autosomal recessive and autosomal dominant inheritance. 2. Explain how Mendel’s experiments followed the inheritance of more than one gene. 3. Explain how the law of independent assortment reflects Loading… the events of meiosis. 4. Explain how pedigrees pedigrees are used to show transmission of single genes. 5. Explain how exome and genome sequencing can reveal whether a sick child with healthy parents inherited two autosomal recessive mutations or has a new, dominant mutation. © McGraw Hill 3  Following the Inheritance of One Gene The World Health Organization estimates that about 10,000 diseases are caused by mutations in single genes, which are called monogenic. About 30 million (1 in 10) people in the United States has a rare disease, as do 350 million people globally Many single-gene diseases affect fewer than 1 in 10,000 individuals. Most familiar, more prevalent illnesses arise from variants in 1 or more genes plus environmental influences © McGraw Hill 4  Characteristics of a Single-Gene Diseases 1 1. In families the probability can be deduced by knowing how the affected person is related to a family member. 2. Tests can sometimes predict the risk of developing symptoms. 3. Loading… The disease may be much more common in some populations than others. 4. The disease may be “fixable” by compensating for the abnormal instructions © McGraw Hill 5  Characteristics of a Single-Gene Diseases 2 Modes of inheritance are the patterns in which single-gene traits and disorders occur in families. Huntington disease is autosomal dominant. Affects both sexes and appears in every generation Cystic fibrosis is autosomal recessive. Affects both sexes and can skip generations through carriers Also called “Mendelian” © McGraw Hill 6  Mendel’s Experiments 1 Described the units of inheritance and how they pass from generation to generation Mendel had no knowledge of D N A, cells, or chromosomes His laws of inheritance explain trait transmission in any diploid species Conducted experiments from 1857 to 1863 on traits in 24,034 plants Peas are ideal for probing heredity © McGraw Hill 7  Mendel’s Experiments 2 Deduced that consistent ratios of traits in the offspring indicated that plants transmitted distinct units His two laws—hypotheses until they had been demonstrated in several species—proposed how this happens. Analyzed genetic crosses P1 = Parental generation F1 = First filial generation F2 = Second filial generation © McGraw Hill 8  Mendel’s Experiments 3 True-breeding—Offspring have the same trait as parent. Example—Short parents produce all short offspring. Hybrids ─ plants that inherit a different gene variant (allele) from each parent. Heterozygote Mendel set up all possible combinations of artificial pollinations: Cross-pollination For example, tall × tall, short × short, tall × short Self-pollination © McGraw Hill 9  Mendel Studied Transmission of Seven Traits in the Pea Plant Access the text alternative for slide images. © McGraw Hill 10  Monohybrid Cross 1 Monohybrid cross follows one trait. The observed trait is dominant. The masked trait is recessive. Loading… © McGraw Hill 11  Monohybrid Cross 2 Follows one trait and the self-crossed plants are hybrids. Parental generation (P1 ) Tall × Short ↓ F1 All tall ↓ F2 1/ 4 Short: 3/4 Tall Access the text alternative for slide images. © McGraw Hill 12  Monohybrid Cross 3 Experiments confirmed that hybrids (heterozygotes) hide one expression of a trait, which reappears when heterozygotes are self-crossed. Mendel speculated: Gametes distribute “elementen” because these cells physically link generations Paired sets of elementen separate as gametes form When gametes join at fertilization, elementen combine anew Law of segregation is Mendel’s idea that elementen separate in the gametes. © McGraw Hill 13  Mendel’s First Law—Segregation 1 Reflects the actions of chromosomes and the genes they carry during meiosis Homozygous carry same alleles TT or tt Heterozygous carry different alleles Tt Genotype = Organism’s alleles Phenotype = Outward expression of an allele combination Wild Type = Most common phenotype Recessive or dominant © McGraw Hill 14  Mendel’s First Law—Segregation 2 Mutant phenotype = Variant of a gene’s expression that arises when the gene undergoes mutation Mendel observed the events of meiosis Two copies of a gene separate with the homologs that carry them when a gamete is produced At fertilization, gametes combine at random © McGraw Hill 15  Mendel’s First Law—Segregation 3 Access the text alternative for slide images. © McGraw Hill 16  Mendel’s Data Table 4.1 Mendel’s Data Demonstrating Segregation Experiment Total Dominant Recessive F2 Phenotypic Ratios 1. Seed form 7,324 5,474 1,850 2.96 : 1 2. Seed color 8,023 6,022 2,001 3.01: 1 3. Seed coat color 929 705 224 3.15 : 1 4. Pod form 1,181 882 299 2.95 : 1 5. Pod color 580 428 152 2.82 : 1 6. Flower position 858 651 207 3.14 : 1 7. Stem length 1,064 787 277 2.84 : 1 Average = 2.98 : 1 © McGraw Hill 17  Punnett Square Represents how genes in gametes join if they are on different chromosomes Access the text alternative for slide images. © McGraw Hill 18  Test Cross 1 A monohybrid cross yields a: 1 TT : 2 Tt : 1 tt genotypic ratio, and 3 tall : 1 short phenotypic ratio Mendel distinguished the TT from Tt tall plants with a test- cross Cross an individual of unknown genotype with a homozygous recessive individual © McGraw Hill 19  Test Cross 2 Access the text alternative for slide images. © McGraw Hill 20  Single-Gene Inheritance Single-gene disorders are rare. Phenotypes associated with single genes are influenced by other genes and environmental factors. Eye color provides a good example of how our view of single-gene traits has evolved with increasing knowledge of our genomes. © McGraw Hill 21  Eye Color 1 People differ in the amount of melanin and number of melanosomes. Have the same number of melanocytes The surface of the back of the iris contributes to the intensity of eye color. O C A2 confers eye color by controlling melanin synthesis. H E R C2 controls expression of the O C A2 gene At least eight other proteins affect eye color © McGraw Hill 22  Eye Color 2 Access the text alternative for slide images. © McGraw Hill 23  Modes of Inheritance Rules that explain the common patterns of single-gene transmission Passing of a trait depends on whether: Gene is on an autosome (chromosomes 1-22) or on a sex chromosome (X and Y) Allele is recessive or dominant Autosomal inheritance can be dominant or recessive © McGraw Hill 24  Comparison of Autosomal Dominant and Autosomal Recessive Inheritance Table 4.2 Comparison of Autosomal Dominant and Autosomal Recessive Inheritance Autosomal Dominant Autosomal Recessive Males and females affected, with equal Males and females affected, with equal frequency frequency Successive generations affected until Can skip generations no one inherits the mutation Affected individual has an affected Affected individual has parents who are parent, unless he or she has a de novo affected or are carriers (heterozygotes) (new) mutation © McGraw Hill 25  Criteria for Autosomal Dominant Traits Males and females can be affected. If a child has the trait, at least one parent also has it. Trait does not skip generations. Example Huntington disease © McGraw Hill 26  Autosomal Dominant Inheritance Access the text alternative for slide images. © McGraw Hill 27  Criteria for Autosomal Recessive Traits Males and females can be affected. Affected males and females can transmit the gene, unless it causes death before reproductive age. Trait can skip generations. Parents of an affected individual are heterozygous or have the trait. Conditions likely to occur in families with consanguinity. Example Cystic fibrosis © McGraw Hill 28  Solving Genetic Problems Follow these five general steps: 1. List all genotypes and phenotypes for the trait. 2. Determine the genotypes of the parents. 3. Loading… Derive possible alleles in gametes. 4. Unite gametes in all combinations to reveal all possible genotypes. 5. Repeat for successive generations. © McGraw Hill 29  On the Meaning of Dominance and Recessiveness Knowing whether an allele is dominant or recessive is important in determining risk inheriting a particular condition. Reflect the characteristics or abundance of a protein Recessive traits are due to “loss of function.” Recessive disorders tend to be severe, produce symptoms earlier than dominant disorders Dominant traits arise from “gain of function.” © McGraw Hill 30  Loss or Gain of a Function Access the text alternative for slide images. © McGraw Hill 31  Mendel’s Second Law—Independent Assortment 1 The inheritance of one does not influence the chance of inheriting the other If the two genes are on different chromosomes If the two genes that are far apart on the same chromosome Numerous crossovers take place between them Independent assortment results from the random alignment of chromosome pairs during metaphase I of meiosis © McGraw Hill 32  Mendel’s Second Law—Independent Assortment 2 Access the text alternative for slide images. © McGraw Hill 33  Plotting a Dihybrid Cross Access the text alternative for slide images. © McGraw Hill 34  Probability The likelihood that an event will occur Product rule—Probability of simultaneous independent events equals the product of their individual probabilities Predicts the chance of parents with known genotypes to produce offspring of a particular genotype Example—Consider the probability of obtaining a plant with wrinkled, green peas (genotype rryy) from dihybrid (RrYy) parents © McGraw Hill 35  Product Rule Do the reasoning for one gene at a time, then multiply the results. Access the text alternative for slide images. © McGraw Hill 36  Using Probability to Track Three Traits Access the text alternative for slide images. © McGraw Hill 37  Pedigree Analysis 1 For researchers and genetic counselors, families are tools The bigger the family, the easier it is to deduce a mode of inheritance. Pedigrees are symbolic representations of family relationships and the transmission of inherited traits. May also include molecular data, test results, and information on variants of multiple genes. © McGraw Hill 38  Pedigree Analysis 2 Access the text alternative for slide images. © McGraw Hill 39  Unusual Pedigrees 1 A partial pedigree of Egypt’s Ptolemy dynasty showing: Genealogy not traits Extensive inbreeding Access the text alternative for slide images. © McGraw Hill 40  Unusual Pedigrees 2 Pedigree showing marriage of first cousins: They share one set of grandparents and, therefore, risk passing on the same recessive alleles to offspring. Access the text alternative for slide images. © McGraw Hill 41  Importance of Pedigrees Today Helps families identify the risk of transmitting an inherited illness Starting points for identifying and describing, or annotating, a gene from the human genome sequence Meticulous family records are helping researchers follow the inheritance of particular genes Example: Mormons and the Amish Very large pedigrees can provide information on many individuals with a particular rare disease © McGraw Hill 42  Autosomal Dominant Trait Does not skip generations, can affect both sexes Polydactyly = Extra fingers and/or toes Access the text alternative for slide images. © McGraw Hill 43  Autosomal Recessive Trait Albinism = Deficiency in melanin production Parents are inferred to be heterozygotes Paul Burns/Digital Vision/Getty Images Access the text alternative for slide images. © McGraw Hill 44  An Inconclusive Pedigree This pedigree can account for either an autosomal dominant or an autosomal recessive trait Inconclusive pedigrees tend to arise when families are small and the trait is not severe enough to impair fertility. Access the text alternative for slide images. © McGraw Hill 45  Conditional Probability Pedigrees and Punnett squares apply Mendel’s laws to predict the recurrence risks of inherited conditions Example: Taneesha’s brother Deshawn has sickle cell disease What is the probability that Taneesha’s child inherits her mutant allele and be a carrier? © McGraw Hill 46  Making Predictions 1 a) Taneesha’s brother, Deshawn, has sickle cell disease. Access the text alternative for slide images. © McGraw Hill 47  Making Predictions 2 Deshawn has sickle cell disease. His unaffected parents, Kizzy and Ike, must both be heterozygous (carriers). Taneesha is also healthy Therefore, she cannot be ss But she could be SS (homozygous normal) or Ss (a carrier) Taneesha’s husband, Antoine, has no family history of sickle cell disease. © McGraw Hill 48  Making Predictions 3 b) Probability that Taneesha is c) If Taneesha is a carrier, a carrier: 2 ⁄ 3 chance that fetus is a carrier: 1 ⁄ 2 Total probability = 2 ⁄ 3 × 1 ⁄ 2 ×2⁄3 Access the text alternative for slide images. © McGraw Hill 49  Exome and Genome Sequencing Clarify Pedigrees 1 An increasingly common clinical scenario occurs when a child has a syndrome not seen before, and both parents are unaffected. Two explanations are possible. Both parents are carriers for recessive mutations in the same gene for a condition that has not yet been identified A de novo (new) dominant mutation arose spontaneously in the sick child, in a sperm or an oocyte © McGraw Hill 50  Exome and Genome Sequencing Clarify Pedigrees 2 Exome and genome sequencing of parents-child “trios” can identify a mutant gene in the affected child Thus can distinguish whether the condition is autosomal recessive and inherited, or autosomal dominant and new. Algorithms compare the D N A sequences of the affected child and unaffected parents Searches for variants of “candidate genes” whose function, or malfunction, might explain the specific symptoms. © McGraw Hill 51  Exome and Genome Sequencing Clarify Pedigrees 3 Access the text alternative for slide images. © McGraw Hill 52  End of Main Content Because learning changes everything.® www.mheducation.com © McGraw Hill LLC. All rights reserved. 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