MBG Lecture 1 cytogenetics-2.pdf

Lecture Objectives: 1.Explain the following terms and their relationship to both genotype and phenotype: chromosome, homologous chromosome, sister chromatid, autosome, bivalent, independent assortment, alignment, segregation, linkage, cis vs trans, and recombination Term Def...

Lecture Objectives: 1.Explain the following terms and their relationship to both genotype and phenotype: chromosome, homologous chromosome, sister chromatid, autosome, bivalent, independent assortment, alignment, segregation, linkage, cis vs trans, and recombination Term Definition Relationship to Relationship to Genotype Phenotype Chromosome A DNA molecule Holds the genotype Influences the containing genetic (alleles of genes) that phenotype through the material, tightly determine the expression of the genes packed in the organism's traits. carried on the nucleus. chromosome. Homologous A pair of Genotype comes from Phenotype is affected chromosome chromosomes, one the alleles present on by the expression of from each parent, each homologous alleles from both with the same genes chromosome, which homologous but possibly different can be identical or chromosomes (e.g., alleles. different dominant or recessive (dominant/recessive). traits). Sister Chromatid Identical copies of a Since they are identical, They do not affect the chromosome, formed sister chromatids have phenotype until they by DNA replication, the same genotype separate during cell held together by a (same alleles of the division to form new centromere. same genes). daughter cells. Autosome Any chromosome that Carries genes that Determines is not a sex contribute to the phenotypic traits that chromosome genotype for most are independent of sex (non-sex traits, excluding those (e.g., eye color, height, determining). linked to sex etc.). chromosomes. Bivalent A pair of homologous Crossing-over between The exchange of chromosomes (each homologous genetic material consisting of two chromosomes can between homologs sister chromatids) create new may result in a novel paired during meiosis combinations of alleles phenotype due to new I. in the genotype of gene combinations. gametes.  Independent The random Creates genetic an result in diverse assortment distribution of diversity in the phenotypes in homologous genotype by shuffling offspring, as different chromosomes into alleles, producing a allele combinations are gametes during unique combination of passed on in each meiosis. chromosomes in gamete. gametes. Alignment The process where Impacts which Random alignment can homologous chromosomes (and influence phenotypic chromosomes line up thus which alleles) are diversity, as it at the metaphase segregated into each determines which traits plate during meiosis I. gamete, affecting the are inherited. genotype of the offspring. Segregation The separation of Ensures that each Incorrect segregation homologous gamete receives one can lead to abnormal chromosomes or copy of each allele, phenotypes, such as sister chromatids into preserving the proper those seen in different gametes. genotype for aneuploidy (e.g., Down inheritance. syndrome). Linkage The tendency of Affects the inheritance Phenotypes may show genes located close pattern of certain linked traits inherited together on the same alleles, as linked genes together (e.g., red hair chromosome to be tend to be passed on and freckles), inherited together together, influencing depending on the gene genotype. linkage. Cis vs. Trans Cis: Alleles of two Cis arrangement keeps Cis may result in traits linked genes on the linked genes together that are inherited same chromosome. in the genotype; Trans together, while Trans Trans: Alleles of arrangement separates can result in mixed linked genes on them, leading to phenotypes for linked opposite different combinations genes. chromosomes. Recombination The exchange of Leads to the creation of Increases the potential genetic material new allele for novel phenotypes between homologous combinations in the as new allele chromosomes during genotype that weren't combinations may lead meiosis. present in either parent. to the expression of different traits. 2.Describe the process of chromosome separation during meiosis and explain how crossing-over contributes to chromosome behavior and repulsion during prophase I ◦Summarize the steps of meiosis with emphasis on chromosome behavior and content Sequential Phases of Meiosis and Major Events Meiosis I: 1. Prophase I: ○ Homologous chromosomes pair up and exchange genetic material (crossing over). ○ The nuclear envelope breaks down, and the spindle forms. 2. Metaphase I: ○ the bivalents positioned with the centromeres of the two homologs on opposite sides of the metaphase plate ○ each bivalent moves onto the metaphase plate, its centromeres are oriented randomly with respect to the poles of the spindle ○ Genes on different chromosomes undergo independent assortment because nonhomologous chromosomes align at random in metaphase I 3. Anaphase I: ○ Homologous chromosomes (not sister chromatids) are pulled to opposite poles. 4. Telophase I: ○ Chromosomes arrive at the poles, chromosomes decondense. ○ Cytokinesis follows, resulting in two haploid daughter cells. Meiosis II: 1. Prophase II: ○ Chromosomes condense again in each haploid daughter cell. ○ The spindle reforms. 2. Metaphase II: ○ Chromosomes align at the metaphase plate. ○ Spindle fibers attach to the centromeres. 3. Anaphase II: ○ Sister chromatids are pulled apart to opposite poles. 4. Telophase II: ○ Chromatids reach the poles and begin to decondense. ○ The nuclear envelope reforms, and cytokinesis follows. 5. Outcome: Four genetically distinct haploid daughter cells are formed.  ◦List the sequential sub-phases of prophase I of meiosis and describe the major events of each sub-phase Subphases of Prophase I in Meiosis Prophase I is a critical stage in meiosis where homologous chromosomes pair up and exchange genetic material. It is divided into five subphases: 1. Leptotene: ○ First step of prophase I ○ Chromosomes begin to condense and become visible ○ Nucleus remains intact, regions of homology are created 2. Zygotene: ○ Second step of prophase I ○ Continued condensation and homolog pairing ○ Homologous chromosomes begin to pair up in a process called synapsis, initiating crossing over ○ Form bilavent = two chromosomes in a synapse 3. Pachytene: ○ Chromosomes condense further, and crossing over occurs. During crossing over, non-sister chromatids of homologous chromosomes exchange genetic material at specific sites called chiasmata. This genetic recombination increases genetic diversity. 4. Diplotene: ○ The synaptonemal complex begins to disassemble via homolog repulsion ○ homologous chromosomes start to separate slightly but remain connected at the chiasmata, where crossing over occurred. ○ Chiasma formed by breakage and rejoining between nonsister chromatids (homologous recombination) ○ chromosomes become more visible, and the chiasmata can be seen as points where the homologous chromosomes are still attached and synaptonemal complex is broken separating arms of the bivalent 5. Diakinesis: ○ Chromosomes condense to their maximum level, becoming shorter and thicker. ○ nuclear envelope begins to break down, and the spindle apparatus starts to form ○ The chiasmata move towards the ends of the chromosomes (terminalization), preparing the chromosomes for segregation. ○ Diakinesis = max force to drive chromosomes apart (max contraction) 3.Explain the concept of regions of homology and how they contribute to chromosome behavior during homologous recombination and separation ◦Define regions of homology and describe how they are generated 1. Defining Regions of Homology and How They Are Generated Regions of homology: specific stretches of DNA sequences that are highly similar or identical between two or more chromosomes. - These regions are critical for accurate genetic recombination and chromosome behavior, especially during meiosis. Generation of Homologous Regions: These regions arise due to the inheritance of genetic material from a common ancestor (mom or dad) - In sexually reproducing organisms, homologous chromosomes (one inherited from each parent) have nearly identical sequences because they carry the same genes in the same order, even though there may be slight variations in the form of alleles. - These similarities allow the chromosomes to recognize each other during synapsis in prophase I of meiosis. 2. Linking Regions of Homology to Chromosome Behavior in Meiosis Homologous Recombination and Alignment: The presence of these homologous regions enables two non-sister chromatids (one from each homologous chromosome) to align properly during meiosis, particularly in Prophase I. The regions of homology play a key role in facilitating homologous recombination through the following processes: 1. Synapsis and Pairing: During the zygotene stage of Prophase I, homologous chromosomes are paired and aligned based on homologous regions. Proteins like the synaptonemal complex represent a very tight association between sister chromatids of each homolog, holding them together. 2. Crossing Over: In the pachytene stage, homologous recombination occurs between these homologous regions. Crossing over involves the exchange of genetic material between non-sister chromatids. This exchange only occurs when regions of high sequence similarity are present, allowing for accurate pairing and alignment. 3. Chiasmata Formation: After crossing over, regions of homology also help maintain physical connections between homologous chromosomes via  chiasmata, where crossover events have occurred and where homologs remain attached to their similar partner, so they are set up for repulsion during diplotene. Metaphase I 1. Genes on different chromosomes undergo independent assortment because nonhomologous chromosomes align at random in metaphase 1 4.Evaluate the processes involved in generating genetic variation in offspring and explain how changes in the steps and stages associated with meiosis affect outcomes ◦Describe the two factors associated with increasing variation of offspring: 1) Crossing-over or Recombination vs. 2) alignment and segregation ◦Explain the process of recombination and the corresponding consequences of different forms of crossing over ◦Explain how alignment and segregation relate to independent assortment ◦List the potential consequences of alignment and segregation for multiple chromosomes Processes Involved in Generating Genetic Variation in Offspring Meiosis is a key driver of genetic variation in sexually reproducing organisms. Two major processes contribute to increasing variation in offspring: crossing-over (recombination) and alignment and segregation during meiosis. 1. Two Factors Associated with Increasing Variation of Offspring 1. Crossing-Over (Recombination) Definition: Crossing-over or recombination refers to the physical exchange of genetic material between non-sister chromatids of homologous chromosomes during Prophase I of meiosis.  Impact on Variation: This process generates new allele combinations in the offspring by mixing maternal and paternal genetic material, leading to genetic diversity. Each chromosome that results from crossing-over is a mosaic of the two homologs, which means that offspring inherit different combinations of genes. 2. Alignment and Segregation Definition: During Metaphase I, nonhomologous chromosome pairs align randomly along the metaphase plate. This alignment determines which chromosomes will segregate to each daughter cell during Anaphase I. Impact on Variation: This randomness in alignment is the basis of independent assortment. Different combinations of maternal and paternal chromosomes can be inherited by the gametes, leading to a high degree of genetic variation. Each gamete receives a unique set of chromosomes. 2. Recombination and Consequences of Different Forms of Crossing-Over Process of Recombination: 1. Recombination between linked genes located on the same chromosome involves homologous crossing over, allelic exchange between them 2. Recombination changes the allele arrangement on homologous Consequences of Different Forms of Crossing-Over: 1. Recombination frequency: is specific for a particular pair of genes 2. Recombination between linked genes: occurs at the same frequency whether alleles are in cis or trans configuration 3. Recombination frequency increases: with increasing distance between genes 4. Maximum recombination frequency: between any two genes is 50% despite distant 3. Alignment, Segregation, and Independent Assortment Alignment in Metaphase I: Homologous chromosomes align at the metaphase plate, and the orientation of each homologous pair is random with respect to the poles of the cell. This random orientation is the basis of independent assortment, where each pair of homologs segregates independently of the others.  Segregation in Anaphase I: Homologous chromosomes are pulled to opposite poles of the cell. This separation is crucial because it ensures that each gamete receives only one chromosome from each homologous pair. Due to the random alignment in Metaphase I, the combination of chromosomes in each gamete is unique, which results in numerous possible combinations of maternal and paternal chromosomes. Independent Assortment: Each chromosome pair segregates independently of the others, resulting in 2ⁿ possible combinations of chromosomes in the gametes, where "n" is the number of chromosome pairs. In humans, this allows for over 8 million different combinations before even considering recombination. 4. Consequences of Alignment and Segregation for Multiple Chromosomes Random Combinations of Parental Chromosomes: Independent assortment ensures that each gamete inherits a random combination of maternal and paternal chromosomes. This randomness is a key factor in generating genetic diversity. Cis configuration: mutant alleles of both genes are on the same chromosome (ab/AB) Trans configuration: mutant alleles are on different homologues of the same chromosome (Ab/aB) Potential Consequences: 1. Duplications: one copy has too much info 2. Deletion: one copy has too little info Deletions are most common genetic abnormality observed clinically In summary, both crossing-over and independent assortment are essential for generating genetic variation, but errors in these processes can lead to significant consequences such as genetic disorders. 5. Assess the consequences for genotype and phenotype with parental and recombinant chromosomes with consideration of cis and trans arrangements Consequences for Genotype and Phenotype with Parental and Recombinant Chromosomes Cis Arrangement Consequences: Genotype: In a cis arrangement, if no recombination occurs, offspring will inherit one set of alleles from each parent as they are (i.e., the alleles linked on the same chromosome are inherited together). ○ The offspring will likely inherit either the combination A B or a b. Phenotype: If the alleles are in a cis arrangement and no crossing-over occurs, the offspring's phenotype will reflect the parental combination of dominant/recessive traits. ○ For example, if A and B are dominant, the offspring may express both traits if they inherit A B. Trans Arrangement Consequences: Genotype: In a trans arrangement, the alleles are mixed between chromosomes (e.g., A b and a B). Without recombination, the offspring will inherit mixed allele combinations such as A b or a B, leading to a different genotype from either parent. Phenotype: The phenotype could be a mix of traits compared to the parents, depending on the interaction of alleles. ○ For example, if A is dominant and b is recessive, and recombination does not occur, the offspring may show the trait associated with A and not with b. Recombination in Cis and Trans Arrangements: Cis Arrangement: If recombination occurs between the two genes on a chromosome, new combinations (recombinant chromosomes) will form, such as A b or a B. This recombination can lead to novel allele combinations in the offspring's genotype, which may result in new phenotypic traits. Trans Arrangement: Recombination in a trans arrangement can restore parental combinations (e.g., A B and a b), but it can also generate novel combinations depending on where crossover happens. Phenotypic Ratios in Recombinant vs. Parental Chromosomes: Recombinant Chromosomes: In a population where recombination occurs, recombinant phenotypes (due to new allele combinations) may appear at a lower frequency compared to the parental phenotypes. This is because recombination between two linked genes is less frequent than inheriting the original parental chromosome. Parental Chromosomes: Offspring inheriting parental chromosomes (without recombination) will tend to display phenotypes similar to the parents. The frequency of these parental types will generally be higher than recombinant types in linked genes. 4. Potential Consequences of Recombination in Cis and Trans Arrangements Increased Genetic Diversity: Recombination in both cis and trans arrangements introduces new allele combinations, enhancing genetic diversity in a population. New Trait Combinations: The interaction between genes in different arrangements can lead to the appearance of new traits or a mix of traits in offspring that differ from both parents, depending on how the alleles influence each other (dominance, epistasis, etc.). Genetic Disorders: In some cases, recombination errors (such as unequal crossing-over) can result in deleterious mutations, which may cause genetic disorders or phenotypic abnormalities. Summary Cis arrangement keeps linked genes inherited together unless recombination occurs, leading to either parental or new recombinant phenotypes depending on crossing-over. Trans arrangement can result in more diverse offspring even without recombination, but recombination can further shuffle alleles to restore parental types or create new genetic combinations. Both recombination and independent assortment contribute to genetic variation in genotype and phenotype, but the arrangement of alleles (cis vs. trans) influences how recombination alters these outcomes.