Bio 342 Lect 2'.pptx

Molecular explanation for Mendel’s pea shape • The R allele encodes Starch branching enzyme (Sbe1). • The r allele does not make Sbe1. Sucrose and unbranched starch build up, leading to wrinkled peas. Access the text alternative for slide images. © McGraw Hill 1 Molecular explanation for Mendel’...

Molecular explanation for Mendel’s pea shape • The R allele encodes Starch branching enzyme (Sbe1). • The r allele does not make Sbe1. Sucrose and unbranched starch build up, leading to wrinkled peas. Access the text alternative for slide images. © McGraw Hill 1 Molecular explanation for Mendel’s pea color • The Y allele encodes the Stay green enzyme (Sgr). Sgr helps break down chlorophyll. • The y allele does not make Sgr. Chlorophyll is not broken down and the peas remain green. Access the text alternative for slide images. © McGraw Hill 2 Two general molecular principles 1. A specific gene determines a specific protein, whose activity may affect the phenotype 2. A dominant allele usually determines a normally functioning protein, and a recessive allele usually does not encode a functional protein © McGraw Hill 3 1.3 Mendelian Inheritance in Humans Learning Objectives: • Analyze human pedigrees to determine whether a genetic disease exhibits recessive or dominant inheritance • Explain why Huntington’s disease is inherited as a dominant allele while cystic fibrosis is caused by a recessive allele © McGraw Hill 4 Some of the most common single-gene traits caused by dominant alleles in humans © McGraw Hill Disease Frequency Chromosome Familial hypercholesterolemia 1/500 19p von Willebrand disease 1/8,000 12p Osteogenesis imperfecta (types IIV) Marfan syndrome 1/10,000 17q,7q 1/10,000 15q Neurofibromatosis type I 1/3,500 17q Huntington chorea 1/15,000 4p Retinoblastoma 1/14,000 13q Some of the most common single-gene traits caused by recessive alleles in humans Disease Frequency Chromosome Cystic fibrosis 1/2,500 7q  -Thalassemia High 16p  -Thalassemia High 11p Sickle cell anemia High 11p Phenylketonuria 1/10,000 12q Gaucher disease 1/1,000 1q Tay-Sachs disease 1/4,000 15q In humans, pedigrees can be used to study inheritance Pedigrees are orderly diagrams of a family's relevant genetic features Includes as many generations as possible (ideally, at least both sets of grandparents of an affected person) Pedigrees can be analyzed using Mendel's laws • Is a trait determined by alternate alleles of a single gene? • Is a trait dominant or recessive? © McGraw Hill 7 Symbols used in pedigree analysis Access the text alternative for slide images. © McGraw Hill 8 Dominant pattern of inheritance Huntington disease • Every affected person has at least one affected parent • Mating between affected person and unaffected person is effectively a testcross Access the text alternative for slide images. © McGraw Hill 9 Recessive trait pattern of inheritance cystic fibrosis Parents of affected individuals are unaffected but are heterozygous (carriers) for the recessive allele Access the text alternative for slide images. © McGraw Hill 10 Characteristics of Autosomal Recessive Inheritance  If it appears in more than one family member, typically it is seen only within a sibship, not in other generations  The recurrence risk for each sib of the proband is 25%  More common with consanguinity, especially for rare diseases  Usually, males and females are equally likely to be affected  New mutation is almost never a consideration Characteristics of Autosomal Dominant Inheritance  The phenotype appears in every generation, each affected person having an affected parent (except with reduced penetrance, new mutation, germline mosaicisim, or anticipation).  Each child of an affected parent has a 50% risk of inheriting the trait.  Unaffected family members do not transmit the phenotype to their children (except with reduced penetrance, new mutation, germline mosaicism, or anticipation).  Males and females are equally likely to transmit the trait, to children of either sex. In particular, there is male-to-male transmission (in contrast to sex-linked recessive inheritance).  New mutations are relatively common, sometimes accounting for up to half or more of all patients, and depends on the fitness of the syndrome. How to recognize dominant traits in pedigrees Three key aspects of pedigrees with dominant traits: 1. Affected children always have at least one affected parent 2. As a result, dominant traits show a vertical pattern of inheritance 3. Two affected parents can produce unaffected children, if both parents are heterozygotes © McGraw Hill 13 How to recognize recessive traits in pedigrees Four keys aspects of pedigrees with recessive traits: 1. Affected individuals can be the children of two unaffected carriers, particularly as a result of consanguineous (between relatives) mating 2. All the children of two affected parents should be affected 3. Rare recessive traits show a horizontal pattern of inheritance 4. Recessive traits may show a vertical pattern of inheritance if the trait is extremely common in the population © McGraw Hill 14 Because learning changes everything. Chapter 02 Extensions to Mendel’s laws Genetics: From Genes to Genomes EIGHTH EDITION Goldberg, Fischer © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. ® Much phenotypic variation poses a challenge to simple Mendelian analysis Many traits exhibit phenotypic patterns that do not follow Mendel’s rules: • No clear dominant or recessive patterns • More than two alleles exist • Multiple genes involved • Gene-environment interactions © McGraw Hill 16 2.1 Extensions to Mendel for single-gene inheritance Learning Objectives: • Categorize allele interactions as completely dominant, incompletely dominant, or codominant • Recognize progeny ratios that imply the existence of recessive lethal alleles • Predict from the results of crosses whether a gene is polymorphic or monomorphic in a population © McGraw Hill 17 Extensions to Mendel for single-gene inheritance 1. Dominance is not always complete • Incomplete dominance • Codominance 2. A gene may have >2 alleles 3. Pleiotropy - one gene may contribute to several characteristics © McGraw Hill 18 Summary of different dominance relationships The phenotype of the heterozygote defines the dominance relationship of two alleles • Complete dominance: Hybrid resembles one of the two parents • Incomplete dominance: Hybrid is intermediate phenotype of parents • Codominance: Hybrid shows traits from both parents (expressivity) Access the text alternative for slide images. © McGraw Hill 19 Flower color in snapdragons is an example of incomplete dominance Crosses of pure-breeding red with pure-breeding white results in all pink (a): Henry Hemming/Moment Open/Getty Images © McGraw Hill 20 Pink flowers in snapdragons are the result of incomplete dominance • • • Phenotype ratios reflect the genotype ratios Access the text alternative for slide images. © McGraw Hill 21 Molecular explanation for incomplete dominance in snapdragon flower color The normal allele produces an enzyme involved in pigment production • • • © McGraw Hill 22 In codominance, the F1 hybrids display traits of both parents 1 Spotted All progeny are spotted and dotted • 1 spotted • 2 spotted and dotted • 1 dotted Phenotype ratios reflect the genotype ratios Access the text alternative for slide images. © McGraw Hill 23 In codominance, the F1 hybrids display traits of both parents 2 Gene I controls the type of sugar polymer on surface of RBCs Two alleles, in different sugars result • • • individuals have both A and B sugars Access the text alternative for slide images. © McGraw Hill 24 Dominance relations between alleles do not affect transmission of alleles • Type of dominance (complete, incomplete dominance, codominance) depends on the type of proteins encoded and the biochemical functions of the proteins • Variation in dominance relations do not negate Mendel's laws of segregation • Interpretation of phenotype/genotype relations is more complex © McGraw Hill 25