Chapter 5 & 6 Non-Mendelian Inheritance PDF

Because learning changes everything. ® Chapter 5 & Chapter 6 (6.1 – 6.2) Chapter 5 Non- Mendelian Inheritance © 2021 McGraw Hill. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitt...

Because learning changes everything. ® Chapter 5 & Chapter 6 (6.1 – 6.2) Chapter 5 Non- Mendelian Inheritance © 2021 McGraw Hill. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw Hill.  Topics What are the four rules of Mendelian inheritance, and what inheritance patterns break these rules? What is the maternal effect? What is epigenetics? What is dosage compensation? What is imprinting? What is extranuclear inheritance (DNA outside the nucleus)? What is gene linkage, and how do genes become unlinked? https://writingyourfirstnovelblog.com/2019/06/13/break-the-rules/ © McGraw Hill 2  What is Epigenetics? https://www.youtube.com/watch?v=_aAhcNjmvhc © McGraw Hill 3  Mendelian Inheritance Conforms to four rules: 1. Expression of the genes in the offspring directly influences their traits 2. Genes are passed unaltered from generation to generation (except when rare mutations occur) 3. Genes obey Mendel’s law of segregation 4. When crosses involve more than one gene, the genes obey Mendel’s law of independent assortment © McGraw Hill 4  Non-Mendelian Inheritance Maternal effect: breaks rule 1 Involve genes in the nucleus Genotype of offspring does not directly govern phenotype Epigenetic inheritance: breaks rule 2 Involve genes in the nucleus Genes are modified (e.g., methylation) Extranuclear inheritance: breaks rule 3 Involves genes in organelles other than the nucleus Linkage (Chapter 6): breaks rule 4 Involves genes in the nucleus Genes do not assort independently © McGraw Hill 5  Maternal Effect Genotype of the mother  determines the phenotype of her offspring Genotypes of the father and offspring themselves do not affect the phenotype of the offspring Due to the accumulation of gene products that the mother provides to her developing eggs Example: water snail, Limnaea peregra Shell and internal organs can be arranged in one of two directions Right-handed (dextral) DOMINANT 1920s y in tt Left-handed (sinistral) Stud. Boyco.E by A © McGraw Hill 6  Figure 5.1 Phenotype of the offspring depended solely on the genotype of the mother DD or Dd mothers  dextral offspring dd mothers  sinistral offspring The genotypes of the father and offspring do not affect the phenotype of the offspring Access the text alternative for slide images. © McGraw Hill 7  The Mechanism of Maternal Effect in Snail Coiling Maturing animal oocytes are surrounded by maternal cells that provide them with nutrients These nurse cells are diploid, whereas the oocyte becomes haploid (Figure 5.2a) (a) Transfer of gene products from nurse cells to egg The nurse cells express mRNA and/or protein from genes of the D allele (green) and the d allele (red) and transfer those products to the egg. Access the text alternative for slide images. © McGraw Hill 8  The Mechanism of Maternal Effect in Snail Coiling (Figure 5.2b) D gene products cause egg cleavage that promotes a right- handed body plan. body plan ail’s The sn depends on re f curvatu ge pattern o ava the cle immediately the egg rtilization after fe (b) Maternal effect in snail coiling Access the text alternative for slide images. © McGraw Hill 9  The Mechanism of Maternal Effect in Snail Coiling Figure 5.2b Recessive d gene products cause egg cleavage that promotes a left- handed body plan. Even if the egg is fertilized by sperm carrying the dominant D allele, the sperm’s genotype is irrelevant Expression of the sperm’s gene  too late to change early embryonic development © McGraw Hill 10  Coiling at the Cellular Level The orientation of the cleavage plane in the earliest stages of development carries through to the adult s e ne ins c t g te ffe pro s in al e n d role n a (c) An explanation of coiling direction a ter RNA rtant of M de po teps s at the cellular level c o im s i en t play early enes g tha the bryo em Figure 5.2c Access the text alternative for slide images. © McGraw Hill 11  Epigenetic Inheritance Pattern in which a modification occurs to a nuclear gene or chromosome that alters gene expression Not permanent Reversible and does not change the DNA sequence 1. Dosage Compensation 2. Genomic Imprinting © McGraw Hill 12  Epigenetics: Dosage Compensation Changes are caused by DNA (e.g., methylation) and chromosomal modifications Occur during oogenesis, spermatogenesis or early embryonic development Purpose = offset differences in the number of active sex chromosomes Depending on the species, dosage compensation occurs via different mechanisms Dosage compensation has been studied extensively in mammals, Drosophila, and Caenorhabditis elegans © McGraw Hill 13  Table 5.1 Mechanisms of Dosage Compensation Among Different Species Sex Chromosomes in: Species Females Males Mechanism of Compensation Placental XX XY One of the X chromosomes in the somatic cells of females is mammals inactivated. In certain species, the paternal X chromosome is inactivated, and in other species, such as humans, either the maternal or paternal X chromosome is randomly inactivated throughout the somatic cells of females. Marsupial XX XY The paternally derived X chromosome is inactivated in the mammals somatic cells of females. Drosophila XX XY The level of expression of genes on the X chromosome in melanogaster males is doubled. Caenorhabditis XX* X0 The level of expression of genes on each X chromosome in elegans hermaphrodites is decreased to 50% of the level occurring on the X chromosome in males. *In C. elegans, an XX individual is a hermaphrodite, not a female. © McGraw Hill 14  Dosage Compensation in Mammals In 1949, Murray Barr and Ewart Bertram identified  highly condensed structure in the interphase nuclei of somatic cells in female cats but not in male cats This structure became known as the Barr body In 1960, Susumu Ohno correctly proposed that the Barr body is a highly condensed X chromosome In 1961, Mary Lyon proposed that dosage compensation in mammals occurs by the inactivation of a single X chromosome in females © McGraw Hill 15  Dosage Compensation in Mammals Occurs by chromosome condensation (Left) a Barr body in a human nucleus after staining with a DNA- specific dye (Right) the same nucleus stained with a yellow fluorescent probe that recognizes Figure 5.3a the X chromosome © McGraw Hill (a, both): Courtesy of I. Solovei, University of Munich (LMU) 16  Dosage Compensation-Chromosome Condensation The mechanism of dosage compensation in mammals  the Lyon hypothesis = X-chromosome inactivation Example: A white and black variegated coat color found in certain strains of mice Mouse with patches of black and white fur © McGraw Hill 17  The Mechanism of X-chromosome Inactivation 1 A female mouse has inherited two X chromosomes: One from its mother that carries an allele conferring white coat color (Xb) One from its father that carries an allele conferring black coat color (XB) Figure 5.4 Random X-chromosome inactivation occurs early in development. Access the text alternative for slide images. © McGraw Hill 18  The Mechanism of X-chromosome Inactivation 2 During X-chromosome inactivation, the DNA becomes highly compacted Most genes on the inactivated X cannot be expressed When this inactivated X is replicated during cell division- Both copies remain highly compacted and inactive X-chromosome inactivation is passed along to all future somatic cells © McGraw Hill 19  The Mechanism of X-chromosome Inactivation Another example of variegated coat color is found in calico cats (b) A calico cat © McGraw Hill (b): ©cgbaldauf/Getty Images 20  Mammalian Cells Allow a Single X to Remain Active Mammalian cells can count their X chromosomes and allow only one of them to remain active Additional X chromosomes are converted to Barr bodies Phenotype Sex Chromosome Number of Barr Composition bodies Normal female XX 1 Normal male XY 0 Turner syndrome (female) X0 0 Triple X syndrome (female) XXX 2 Klinefelter syndrome (male) XXY 1 © McGraw Hill 21  X-chromosome Inactivation X-chromosome inactivation (XCI) in mammals depends on the X-inactivation center and Xist X-inactivation center (Xic) - short region on the X chromosome © McGraw Hill 22  The Function of the Xic during X-chromosome Inactivation Nucleation: - during embryonic development. Number of X-inactivation centers (Xics) is counted One of the X chromosomes is targeted for inactivation. Spreading: - during embryonic development. Begins at the Xic Progresses toward both ends until the entire chromosomes is inactivated  becomes a Barr body. Maintenance: - from embryonic development through adult life. Inactivated X chromosomes is maintained during cell divisions. Figure 5.7 Access the text alternative for slide images. © McGraw Hill 23  Some Genes May Escape Inactivation Some genes on the inactivated X chromosome are expressed in the somatic cells of adult female mammals Pseudoautosomal genes Dosage compensation in this case is unnecessary because these genes are located on both the X and Y chromosomes Up to a quarter of X-linked genes in humans may escape full inactivation © McGraw Hill 24  Genomic Imprinting Segment of DNA is marked and the effect is maintained throughout the life of the organism that inherited the marked DNA Depending on how the genes are “marked”, the offspring expresses either the maternally-inherited or the paternally- inherited allele Not both This is termed monoallelic expression © McGraw Hill 25  Mouse Igf2 Gene as an Example of Genomic Imprinting The Igf2 gene encodes a growth hormone called insulin-like growth factor 2 A functional Igf2 gene is necessary for a normal size Imprinting results in the expression of the paternal but not the maternal allele The paternal allele is transcribed into RNA The maternal allele is not transcribed Igf2− is a loss-of-function allele that does not express a functional Igf2 protein This may cause a mouse to be dwarf depending on whether it inherits the mutant allele from its father or from its mother © McGraw Hill 26  Igf2 Imprinting (Figure 5.8) Reciprocal cross: Offspring genotypes are identical; phenotypes different © McGraw Hill (photo): Courtesy of Dr. Argiris Efstratiadis 27  Stages of Imprinting At the cellular level: 1. Establishment of the imprint during gametogenesis 2. Maintenance of the imprint during embryogenesis and in the adult somatic cells 3. Erasure and reestablishment of the imprint in the germ cells Access the text alternative for slide images. Figure 5.9 © McGraw Hill 28  Genomic Imprinting Occurs in Several Species Insects, mammals and flowering plants It may involve A single gene A part of a chromosome An entire chromosome Even all the chromosomes from one parent It can be used for X inactivation in some species © McGraw Hill 29  Imprinting and DNA Methylation Genomic imprinting must involve a marking process Involves an imprinting control region (ICR) located near the imprinted gene The ICR is methylated either in the oocyte or sperm Not both The ICR contains binding sites for one or more transcription factors that regulate the imprinted gene For most genes, methylation causes inhibition of transcription © McGraw Hill 30 Figure 5.10 Each parent inherits one methylated and one unmethylated gene, which is maintained in somatic cells. Methylation is removed in gamete forming cells Access the text alternative for slide images. © McGraw Hill 31  Imprinting in Human Disease Most commonly, PWS and AS Prader-Willi syndrome (PWS) involve a small deletion in chromosome 15 PWS is characterized by If it is inherited from the Reduced motor function father  PWS Obesity If it is inherited from the mother  AS Small hands and feet Angelman syndrome (AS) AS is characterized by Hyperactivity and thinness Unusual seizures Repetitive symmetrical muscle movements Mental deficiencies © McGraw Hill 32  Imprinted Genes Cause AS or PWS Researchers have discovered that this region contains closely linked but distinct genes These are maternally or paternally imprinted AS results from the lack of expression of a single gene, UBE3A UBE3A encodes a protein that regulates protein degradation The paternal copy is silenced © McGraw Hill 33  Imprinted Genes Cause AS or PWS PWS appears to result from the lack of expression of several genes: SNRNP encodes a small nuclear ribonucleoprotein polypeptide N which is part of a complex that controls gene splicing NDN encodes a protein that functions as a growth suppressor for neurons A cluster of genes that encode snoRNAs The maternal copy of each of these genes is silenced © McGraw Hill 34  Figure 5.11 Video Link: Prader-Willi Syndrome https://www.youtube.com/watch?v=8CK N6idlE80 Access the text alternative for slide images. © McGraw Hill 35  Extranuclear Inheritance Extranuclear inheritance = inheritance patterns involving genetic material outside the nucleus Mitochondria and chloroplasts These organelles are found in the cytoplasm Extranuclear inheritance is also termed cytoplasmic inheritance © McGraw Hill 36  Genetic Material of Mitochondria and Chloroplasts Found in nucleoid The genome is composed of a single circular chromosome containing double-stranded DNA (a): From: Prachar J., “Mouse and human mitochondrial nucleoid--detailed structure in relation to function,” Gen Physiol Biophys. 2010 Jun, 29(2): 160-174. Fig 3A; (b): ©Dr Jeremy Burgess/Science Source © McGraw Hill 37  Genetic Material of Mitochondria and Chloroplasts Note: A nucleoid can contain several copies of the chromosome An organelle can contain more than one nucleoid Chloroplasts tend to have more nucleoids per organelle than mitochondria TABLE 5.3 Genetic Composition of Mitochondria and Chloroplasts Organism(s) Organelle Nucleoids per Number of Chromosomes Organelle per Nucleoid Tetrahymena Mitochondrion 1 6 to 8 Mouse Mitochondrion 1 to 3 2 to 6 Chlamydomonas Chloroplast 5 to 6 ∽15 Euglena Chloroplast 20 to 34 10 to 15 Flowering plants Chloroplast 12 to 25 3 to 5 Source: Gillham, Nicholas W., Organelle Genes and Genomes. New York, NY: Oxford University Press, 1994. © McGraw Hill 38  Figure 5.13 Mitochondrial DNA The human mitochondrial DNA (mtDNA) consists of only 17,000 bp Most mitochondrial proteins are encoded by genes in the nucleus These proteins are made in the cytoplasm, then transported into the mitochondria Access the text alternative for slide images. © McGraw Hill 39  Chloroplast DNA The genetic material in chloroplasts is referred to as cpDNA It is typically about 10 times larger than the mitochondrial genome of animal cells As with mitochondria, many chloroplast proteins are encoded by genes in the nucleus These proteins contain chloroplast-targeting signals that direct them from the cytoplasm into the chloroplast © McGraw Hill 40  Maternal inheritance Carl Correns discovered that pigmentation in Mirabilis jalapa (the four o’clock plant) shows a non-Mendelian pattern of inheritance Leaves could be green, white or variegated (with both green and white sectors) Correns determined that the pigmentation of the offspring depended solely on the maternal parent and not at all on the paternal parent This is termed maternal inheritance Different than maternal effect! © McGraw Hill 41  Figure 5.14 Maternal inheritance occurs because the chloroplasts are transmitted only through the cytoplasm of the egg The pollen grains do not transmit chloroplasts to the offspring Phenotype of leaves determined by the types of chloroplasts found in leaf cells Access the text alternative for slide images. © McGraw Hill 42  Figure 5.15 Green phenotype is the wild-type Due to normal chloroplasts that can make green pigment White phenotype is the mutant Due to a mutation that prevents the synthesis of the green pigment Variegated phenotype A cell can contain both types of chloroplasts This condition termed heteroplasmy © McGraw Hill 43  The Pattern of Inheritance of Organelles The pattern of inheritance of mitochondria and chloroplasts varies among different species Heterogamous species Produce two kinds of gametes Female gamete  Large Provides most of the cytoplasm to the zygote Male gamete  Small Provides little more than a nucleus In these species, organelles are typically (but not always) inherited from the mother © McGraw Hill 44  The Pattern of Inheritance of Organelles Species with maternal inheritance may, on occasion, exhibit paternal leakage The paternal parent occasionally provides mitochondria through the sperm In the mouse, for example, 1 to 4 paternal mitochondria are inherited for every 100,000 maternal mitochondria per generation of offspring © McGraw Hill 45  Table 5.4 Transmission of Organelles Among Different Organism Organism Organelle Transmission S. Cerevisiae (Yeast) Mitochondria Biparental inheritance Molds Mitochondria Usually maternal inheritance; paternal inheritance has been found in the genus Allomyces Chlamydomonas (Alga) Mitochondria Chlamydomonas exists in two mating types (mt+ and mt−). Inherited from the parent with the mt- mating type Chlamydomonas Chloroplasts Inherited from the parent with the mt+ mating type Angiosperms (Plants) Mitochondria and chloroplasts Often maternal inheritance, although biparental inheritance is among some species Gymnosperms (Plants) Mitochondria and chloroplasts Usually paternal inheritance Mammals Mitochondria Maternal inheritance © McGraw Hill 46  Human Mitochondrial Diseases Occurs in two ways Human mtDNA is transmitted from mother to offspring via the cytoplasm of the egg Therefore, the transmission of human mitochondrial diseases follows a strict maternal inheritance pattern Mitochondrial mutations may occur in somatic cells Accumulate as a person ages Mitochondria are very susceptible to DNA damage High oxygen consumption leads to free radicals Mitochondrial DNA has very limited repair abilities © McGraw Hill 47  Table 5.5 Examples of Human Mitochondria Diseases Disease Mitochondrial Gene Mutated Leber hereditary optic neuropathy A mutation in one of several mitochondrial genes that encode respiratory chain proteins: ND1, ND2, CO1, ND4, ND5, ND6, and cytb; tends to affect males more than females Neurogenic muscle weakness A mutation in the ATPase6 gene that encodes a subunit of the mitochondrial ATP-synthetase, which is required for ATP synthesis Mitochondrial myopathy A mutation in a gene that encodes a tRNA for leucine Maternal myopathy and cardiomyopathy A mutation in a gene that encodes a tRNA for leucine Over 200 human mitochondrial diseases have been identified These are typically chronic degenerative disorders affecting cells requiring high levels of ATP such as nerve and muscle cells © McGraw Hill 48  Heteroplasmy in Mitochondrial Disease Heteroplasmy is an important factor in mitochondrial disease Cells can contain a mixed population of mitochondria Some may carry disease causing mutation while others do not As cells divide some cells may receive a high ratio of mutant to normal mitochondria Disease may occur when the ratio of mutant to normal mitochondria exceeds a threshold value Symptoms may vary widely within a given family © McGraw Hill 49  Figure 5.16 The endosymbiosis theory describes the evolutionary origin of mitochondria and chloroplasts These organelles originated when bacteria took up residence within a primordial eukaryotic cell Chloroplasts originated as cyanobacterium Mitochondria originated as Gram-negative nonsulfur purple bacteria During evolution, the characteristic of the intracellular bacterial cell gradually changed to that of the organelle Access the text alternative for slide images. © McGraw Hill 50  Because learning changes everything. ® Chapter 6 Genetic Linkage and Mapping in Eukaryotes Sections 6.1 – 6.2 © 2021 McGraw Hill. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw Hill.  Overview of Linkage Eukaryotic species - linear chromosomes  typically contains many hundred or even a few thousand different genes Synteny = two or more genes are located on the same chromosome and are physically linked Genetic Linkage - genes close together on a chromosome tend to be transmitted as a unit, which influences inheritance patterns https://www.shmoop.com/study-guides/biology/genetics/genetic-linkages © McGraw Hill 52  Linkage Groups Chromosomes are called linkage groups  they contain a group of genes that are linked together The number of linkage groups = the number of types of chromosomes of the species For example, in humans: 22 autosomal linkage groups An X chromosome linkage group A Y chromosome linkage group © McGraw Hill 53  Linkage Groups A two-factor cross studies linkage between two genes A three-factor cross studies linkage between three genes Genes that are far apart on the same chromosome may independently assort from each other due to crossing over https://ib.bioninja.com.au/standard-level/topic-3-genetics/33-meiosis/crossing-over.html © McGraw Hill 54  Independent Assortment does not Always Occur 1905 - William Bateson & Reginald Punnett conducted a two-trait cross in sweet pea Flower color and pollen shape Expected phenotypic ratio in the F2 generation = 9:3:3:1 Did not occur! Access the text alternative for slide images. © McGraw Hill 55  Independent Assortment does not Always Occur 2 F2 generation Observed Ratio Expected Ratio number number Purple flowers, long pollen 296 15.6 240 9 Purple flowers, round pollen 19 1.0 80 3 Red flowers, long pollen 27 1.4 80 3 Red flowers, round pollen 85 4.5 27 1 Bateson & Punnett suggested that the transmission of the two traits from the parents was somehow coupled They did not realize that the coupling is due to the linkage of the two genes on the same chromosome © McGraw Hill 56  Relationship between Linkage and Crossing Over In diploid eukaryotic species, linkage can be altered during meiosis as a result of crossing over Occurs during prophase I of meiosis Replicated sister chromatid homologues associate as bivalents Non-sister chromatids of homologous chromosomes exchange DNA segments Crossing over may produce recombinant genotypes © McGraw Hill 57  Without Crossover Linked Genes Segregate Together The haploid cells contain the same combination of alleles as the original chromosomes The arrangement of linked alleles has not been altered in the gametes Two possible combinations  © McGraw Hill 58  Crossing Over Can Reassort Alleles Haploid cells that contain a combination of alleles NOT found in the original chromosomes are call Four possible nonparental or combinations  recombinant cells Access the text alternative for slide images. © McGraw Hill 59  Morgan’s Evidence for X-linked Genes The first direct evidence of linkage came from studies conducted by Thomas Hunt Morgan Morgan investigated different traits that followed an X-linked pattern of inheritance in Drosophila, including: Body color (Gray/yellow) Eye color (Red/white) Wing length (Long/miniature) © McGraw Hill 60  Morgan’s Three-Factor Cross Access the text alternative for slide images. © McGraw Hill 61  Morgan’s Three-Factor Cross F2 generation Females Males Total Gray body, red eyes, long wings 439 319 758 Gray body, red eyes, miniature wings 208 193 401 Gray body, white eyes, long wings 1 0 1 Gray body, white eyes, miniature wings 5 11 16 Yellow body, red eyes, long wings 7 5 12 Yellow body, red eyes, miniature wings 0 0 0 Yellow body, white eyes, long wings 178 139 317 Yellow body, white eyes, miniature wings 365 335 700 © McGraw Hill 62  Morgan’s Evidence for X-linked Genes Morgan had to interpret two key observations: 1. Why did the F2 generation have a significant number of recombinant offspring? 2. Why was there a quantitative difference between the different types of F2 recombinant offspring? © McGraw Hill 63  Morgan’s Hypotheses Morgan made three important hypotheses to explain his results 1. The genes for body color, eye color and wing length are all located on the X-chromosome, so their alleles will tend to be inherited together 2. Due to crossing over, the homologous X chromosomes (in the female) can exchange pieces of the chromosomes, resulting in new combinations of alleles 3. The likelihood of crossing over depends on the distance between the two genes, and is more likely to occur between two genes that are far apart from each other © McGraw Hill 64  Morgan’s Data Simplified into Gene Pairs Let’s first consider Morgan’s experiments by simplifying the data into gene pairs Gray body, red eyes 1159 Yellow body, white eyes 1017 Gray body, white eyes 17 Recombinant Yellow body, red eyes 12 offspring Total 2205 Red eyes, long wings 770 White eyes, miniature wings 716 Red eyes, miniature wings 401 Recombinant White eyes, long wings 318 offspring Total 2205 © McGraw Hill 65  Nonrecombinant and Recombinant Offspring No crossing over, nonrecombinant offspring © McGraw Hill 66  Nonrecombinant and Recombinant Offspring 2 Crossing over, recombinant offspring © McGraw Hill 67  Morgan’s Explanation for Different Proportions of Recombinant Offspring Now let’s consider the results for all three genes (a) No crossing over in this region, very common © McGraw Hill 68  Morgan’s Explanation for Different Proportions of Recombinant Offspring (b) Cross over between eye color and wing length genes, fairly common © McGraw Hill 69  Morgan’s Explanation for Different Proportions of Recombinant Offspring (c) Crossover between body color and eye color genes, uncommon © McGraw Hill 70  Morgan’s Explanation for Different Proportions of Recombinant Offspring (d) Double crossover, very uncommon © McGraw Hill 71  Ch 5, 6.1 – 6.2 Study Guide Recognize the four rules of Mendelian inheritance and recognize inheritance patterns that deviate Define Maternal Effect Predict outcomes of crosses for genes exhibiting maternal effect Define Epigenetics Compare & contrast mechanisms of dosage compensation in different species Describe the process of X-chromosome inactivation in mammals and explain how it affects female phenotypes Define Genomic Imprinting and predict outcome of crosses for genes involved Explain the molecular mechanism of imprinting Describe how monoallelic expression occurs Describe the role of DNA methylation in gene regulation Describe how imprinting is related to the diseases of Angelman Syndrome and Prader-Willi Syndrome. Describe inheritance patterns of each disease. Define Extranuclear Inheritance Describe general features of chloroplast and mitochondrial genomes Predict outcomes of crosses involving extranuclear inheritance Describe how mutations in mitochondrial genes cause disease in humans Describe the origins of chloroplast and mitochondria (endosymbiotic theory) Differentiate maternal inheritance and maternal effect Define heteroplasmy and paternal leakage Define Genetic Linkage explain how linkage affects the outcomes of crosses Describe how crossing over produces recombinant offspring and how distance between genes affects likelihood of crossing over © McGraw Hill 72  End of Main Content Because learning changes everything. ® www.mheducation.com © 2021 McGraw Hill. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw Hill.