BMS 532 Lecture Packet PDF

Merged Lecture Packet MBG Block 2 10/2/24 to 10/4/24 A way to save time swapping between content… LO1, LO5 Probability Rules Addition Rule: ◦The probability of obtaining one or the other of two mutually exclusive even...

Merged Lecture Packet MBG Block 2 10/2/24 to 10/4/24 A way to save time swapping between content… LO1, LO5 Probability Rules Addition Rule: ◦The probability of obtaining one or the other of two mutually exclusive events is the sum of their individual probabilities Multiplication Rule: ◦The probability of two independent events occurring simultaneously equals the product of their individual probabilities You have actually been doing this for years. We are simply naming the rules and discussing how they work in Genetics analysis. LO1, LO5 When to use each rule… Good rule of thumb to use when determining which rule is preferable: ◦ AND versus OR ◦ AND = multiplication rule OR = addition rule If only one option of 2 is possible in a given question = OR If multiple events that are independent or combine repeated events = AND What is the chance that a male and then a female will be born? ◦ Male vs female = OR = addition rule 1 out of 2 ◦ First a male then a female = AND = multiplication rule of the 2 individual probabilties LO1, LO5 Addition Rule The probability of obtaining one or the other of 2 mutually exclusive events, A or B, is the sum of the separate probabilities Probability of WW or Ww = Probability of WW + Probability of Ww Every time you use a punnet square and say the probabilities of getting particular phenotypes, you are using the ADDITION RULE! LO1, LO5 Product Rule The probability that two or more What is the probability that a independent outcomes will occur is couple’s first 3 children will exhibit a equal to the product of their recessive trait if both parents are individual probabilities heterozygotes? Aa X Aa Use Punnett Squares! What is the probability of aa? Then what is the probability of aa 1. Calculate the individual happening 3 times? probabilities ◦ Probability 1 x 2 x 3 2. Multiply the individual probabilities LO1, LO5 Product Rule Can be used to predict the outcome of a cross involving two or more genes AaBbCC X AabbCc What is the probability that the offspring will be AAbbCc? Probability of AA? Probability of bb? Probability of Cc? P = pAA x pbb x pCc LO1, LO5 More Complex Probabilities X Consider Mendel’s cross of two heterozygous tall plants. What is the likelihood of having three offspring where two are normal height and one is short? This is more difficult because there are multiple ways this could occur with three offspring. Tall could be TT or Tt = 1/4 + 1/2 = 3/4 or Short must be 1/4. Each grouping is 3/4 x 3/4 x 1/4 = 9/64. 9/64 + 9/64 + 9/64 = 27/64. This can become or tedious. 7 Sex-Linked Heredity and Sex Determination BMS 532 BLOCK 2 LECTURE 6  Objectives 1. Define the following terms: homogametic, heterogametic, hemizygous, haploinsufficiency, nondisjunction, genic, environmental, and sexual determination. 2. Compare and contrast sex chromosomes and sex determination across species 3. Explain the distinction between a homogametic and heterogametic individual in XX/XY and ZZ/ZW sex determination 4. Assess the outcomes for a given mating under XX/XY and ZZ/ZW organisms in terms of biological sex expectations and features associated with or influenced by sex chromosomes 5. Evaluate the consequences of changes in genes, environment, and sex chromosome content for sex determination and development of secondary sexual characteristics ◦ Outline how climate change is proposed to be altering male:female ratios in turtles, alligators and crocodiles 6. Compare and contrast the X and Y chromosomes 7. Explain why it is necessary to have regions of similarity between the human X and Y chromosomes 8. Using the Morgan Fruit Fly experiments as a foundation, assess outcomes for a given mating and explain the role of reciprocal crosses in defining sex-linked inheritance ◦ Summarize Morgan’s and Bridge’s fruit fly experiments and their outcomes 9. Explain X-linked inheritance in terms of human health and disease and Explain the consequences for nondisjunction in terms of genotype and phenotype 10. **Determine probabilities for offspring inheriting a particular trait (autosomal vs. sex-linked) LO1 Terminology Sex Chromosomes = chromosomes that contain the genetic information necessary to confer biological sex and influence development of secondary sexual characteristics Homogametic = has gametes with the same sex chromosomes Heterogametic = has gametes with different sex chromosomes Hemizygous = containing only 1 copy of a chromosome that can be or is typically observed in a pair Haploinsufficiency = loss of 1 copy results in a situation where the remaining copy cannot compensate and make sufficient product; reduced function is expected due to the insufficient levels of product ◦ NOTE: genes exclusive to the Y or X in humans are NOT haploinsufficient as proper gene dosage is 1 ◦ This is why some genes on the X MUST be inactivated (see epigenetics lecture) LO2 Sex Chromosomes and Sex Determination In sexual reproduction, differences between the 2 sexes are established by key genes often located on specific sex chromosomes Sex chromosomes can vary across different organisms Sex chromosomes do NOT have to involve 2 distinct chromosome types in the pair ◦ Humans: XX females vs XY males ◦ Grasshoppers: XX females vs XO males (males have fewer chromosomes than females) When the chromosome pairing involves one biological sex having fewer chromosomes, meiosis will result in gametes that have unequal chromosome numbers LO1, LO2, LO3, LO4 More on Sex Chromosomes and Sex Determination Heterogametic Sex = sex with 2 different chromosomes ZZ vs ZW ◦In many species, the heterogametic sex is the female ◦This system is found in birds, snakes, butterflies, some amphibians and some fish LO1, LO3, LO4 XY Heredity (Humans) In humans, males are heterogametic X and Y can pair during Meiosis because of structural similarity in the chromosomes (regions of homology) ◦ Pseudoautosomal regions Crossing-over occurs in these regions Because these are regions of similarity that do contain genes, these regions escape X- inactivation ensuring proper gene dosage for those genes LO1, LO2, LO5 Sex Determination without Sex Chromosomes (Genic or Environmental) While biological sex is frequently determined by genes, the location of those genes can very especially if there are no sex chromosomes ◦No visible difference in the chromosomes of males and females and no sex chromosomes Genic Determination ◦Genes at one or more loci determine sex without specific sex chromosomes LO1, LO2, LO5 Sex Determination without Sex Chromosomes (Genic or Environmental) Environmental Sex Determination ◦Environment is either partially or completely responsible for sex determination ◦Organism has equal chance to be either sex but cannot be both at the same time ◦Ex: slipper limpet (Crepidula fornicata) ◦Sequential hermaphroditism LO1, LO2, LO5 Sex Determination without Sex Chromosomes (Genic or Environmental) Environmental Sex Determination ◦Reptiles including turtles, crocodiles, alligators and some birds ◦ Temperature-based sex determination https://www.sciencedirect.com/science/article/abs/pii/S0006320717308534 LO1, LO2, LO5 Sex Determination without Sex Chromosomes (Genic or Environmental) Environmental Sex Determination ◦ For turtles, warmer temperatures result in more females, colder temperatures yield more males ◦ For alligators, colder temperatures result in more females, warmer temperatures yield more males ◦ For bearded dragon lizards, environment influences the phenotype rather than the genotype. ◦ ZZ is male except when the embryo is incubated at high temperatures, then ZZ is phenotypically female even though genotypical male. https://www.sciencedirect.com/science/article/pii/B9780123749307100019 LO1, LO2, LO5 Sex Determination without Sex Chromosomes (Genic or Environmental) Environmental Sex Determination ◦Crocodiles ◦Sex determination is more complex ◦32-33°C nest temperature = male crocs ◦Any other temperature = females https://www.sciencedirect.com/science/article/pii/B9780123749307100019 LO1, LO2, LO5 Global Warming and Sex Determination Increasing global temperatures for sex determination based on temperature is altering the ratio of males to females and disrupting reproductive potential All Mal e All Femal e https://onlinelibrary.wiley.com/doi/full/10.1111/eva.13226 LO1, LO2 Mammalian Biological Sex Determination Genes typically located on the Y chromosome confer key proteins for defining the production of testes Loss of genes in an XY individual will result in phenotypical development as female Phenotypic development as female with functional ovaries in the absence of genes is not guaranteed thus there is no actual biological default sex as previously thought Presence of small portions of the Y chromosome in XX individuals has been shown to be sufficient to cause phenotypical male development implying only a small portion of the chromosome is actually needed for sex determination LO1, LO2, LO6 Human Biological Sex Determination SRY gene on Y chromosome confers testes development ◦ Transcription factor ◦ Activation of the gene occurs at roughly 6 weeks development ◦ Prior to the activation of key genes gonads are undifferentiated ◦ SRY is located in close proximity to the pseudoautosomal region Once triggered, testes begin to form and secrete ◦ Testosterone to promote development of male characteristics and ◦ Mullerian inhibitory substance (MIS) to suppress/degenerate female reproductive ducts In the absence of SRY, ovaries can develop (estrogen and no MIS) Absence of proper gene activity can hinder development and result in sterility LO6, LO7 More about the X and Y Chromosomes Although the main components of sex determination are located on these chromosomes, autosomal genes are also important ◦ There are actually more genes associated with sexual development on the autosomes but they require activation typically triggered by the genes on the sex chromosomes The X and Y chromosomes also contain genes NOT associated with sexual development ◦ The inheritance of those genes do not follow Mendel’s laws Males in XY inheritance are hemizygous (only one copy of some genes) LO6, LO7 More on Pseudoautosomal Regions Distal region of short arms of X and Y = highly similar DNA sequences (PAR1) ◦ Areas for crossing over in male meiosis that resembles autosomal crossing-over Region of homology at distal end of long arms that also experience alignment and crossing-over (PAR2) All genes within PAR1 are NOT inactivated in women ◦ Need 2 copies (dosage compensation) There is a high recombination frequency in PAR1 LO1, LO2, LO3, LO4 Summary LO1, LO2, LO8 Sex-Linked Inheritance Inheritance patterns for genes on the sex chromosomes differs from that for autosomes Since the X chromosome has more genes located on it, most sex-linked inheritance is condensed to X-linked inheritance Sex-linked inheritance results in differential expression of traits between males and females Thomas Hunt Morgan and his fruit fly experiments were a major series of experiments demonstrating X-linked inheritance with differential expression of traits between males and females LO8, LO9 Morgan’s Crosses Parental Generations 2 crosses that are reciprocal parents are needed to define X-linked inheritance ◦ 1) Red-eyed female x White-eyed male ◦ Offspring = All Red Eyes (no difference between males and females) ◦ Morgan then took these offspring (F1) and crossed them (generated F2) ◦ 2) White-eyed female x Red-eyed male ◦ Offspring = All Red-eyed Females and All White-eyed males ◦ Morgan then took these offspring (F1) and crossed them (generated F2) 26  Morgan’s Crosses F1 crosses ◦ 1) Heterozygous Female x Red-eyed Male ◦ All females red-eyed ◦ Half the males white-eyed ◦ 2) Heterozygous Female x White-eyed Male ◦ 50% red-eyed males and females ◦ 50% white-eyed males and females The discrepancy between males and females in presentation of the phenotype is a hallmark of X- linked or sex-linked inheritance 27 LO8, LO9 LO8, LO9 Morgan’s Fruit Fly Experiments Summary Morgan’ s genetic principles: Sex-linked inheritance based on mutations observed in males only Gene linkage based on the inheritance of genes as a single unit Chromosome mapping based on recombination frequencies between linked genes  Deviations from Expectations Morgan’s cross shown here should produce 100% red eyed F1 flies. Out of 1237 F1 flies screened, 1234 had red eyes ◦ Three white-eyed male flies were observed Further similar crosses continued to produce a low frequency of white-eyed males that was too high to be explained by random mutation. Calvin Bridges was assigned by Morgan to work on the problem LO8, LO9 29  Bridge’s Experiments in Fruit LO8, LO9 Flies: Nondisjunction After repeating several crosses similar to Morgan’s, Bridge discovered that only certain matings produced the unexpected results Bridges hypothesized that the exceptional white-eyed female strain possessed two X chromosomes and a Y chromosome. ◦ XXY flies develop as females and can exhibit recessive traits Bridges proposed that about 10% of the time during meiosis, the two X chromosomes fail to separate from each other ◦ Failure to properly separate chromosomes = Nondisjunction LO8, LO9 Nondisjunction More evidence for the chromosome theory of inheritance Failure to properly separate chromosomes leads to inappropriate gene content in the offspring Many of the genetic options produce nonviable offspring (embryonic lethal) ◦ YY (always) and XXX (usually) Principles and Processes of Epigenetics CHANGES IN GENE EXPRESSION WITHOUT CHANGING THE GENETIC CODE BMS 532 BLOCK 2 LECTURE 7  Objectives 1. Define the following terms: epigenetics, euchromatin, heterochromatin, imprinting, and X-inactivation/Lyonization 2. Compare and contrast euchromatin and heterochromatin and Compare and contrast constitutive and facultative heterochromatin 3. Summarize the process of Methylation and Chromatin remodeling and Compare and contrast DNA and histone methylation ◦ Identify the role of the following players: CRCs, Histone methyltransferases, DNA methyltransferases, and histone deacetylases 4. Outline the importance of heterochromatin to gene regulation and chromosome function and the role remodeling plays in development 5. Assess the consequences for gene regulation following or as induced by changes in chromatin structure 6. Evaluate imprinting and the role of imprinting in gene regulation and human health ◦ Define imprinting and differentially methylated regions ◦ Compare and contrast maternal and paternal imprinting ◦ Explain the process of imprinting in gametogenesis ◦ Summarize the role of demethylation and re-methylation in imprinting ◦ Compare and contrast Prader-Willi and Angelman Syndromes in terms of inactivation, loss of genetic information, and genes involved in the disorders (from the perspective of which are expressed and which are lost) 7. Evaluate lyonization/x-inactivation in terms of process and effects on gene expression ◦ Explain the process of lyonization/X-inactivation and its connection to inactive chromatin ◦ Compare and contrast imprinted lyonization from random lyonization ◦ Summarize the process of x-inactivation and explain the role of mRNA in the process ◦ List and explain the consequences/effects of X-inactivation (define dosage compensation and explain its role in proper cell function) 8. Define mosaicism and explain the role of x-inactivation in generating mosaic phenotypes LO1 Terminology Epigenetics ◦ The study of the manner in which expression of heritable genetic traits are modified by environmental influences or other mechanisms without a change in DNA sequence Euchromatin ◦ The state of chromatin in which it is partially or fully uncoiled and genetically active; light- staining Heterochromatin ◦ The state of chromatin in which it is tightly coiled and considered molecularly inactive; dark- staining ◦ Constitutive Chromatin ◦ Region of heterochromatin that is never transcribed ◦ Facultative Chromatin ◦ Region of heterochromatin that is silenced and can become active ◦ Regions that become heterochromatic in certain cells/tissues Lyonization/X-Inactivation ◦ Inactivation of genes on the X chromosome that exhibit dosage effects LO1, LO2 Euchromatin Loosely coiled during interphase ◦Beads-on-a-string conformation Condensed during mitosis Often undergoing active transcription G-banding: Light Bands LO1, LO2 Heterochromatin Late Replicating; highly inaccessible by the replication machinery Remains condensed from prophase through the mitotic cycle Can be constitutive or facultative NOT transcriptionally active G-banding: dark bands LO1, LO3, LO4, DNA Methylation LO5 Addition of methyl group to cytosine or adenine DNA bases Cytosine methylation is associated with heterochromatin formation and repression of gene expression Important process in epigenetics and in genetic disease LO3, Ability of a methylated DNA to influence an adjacent promoter is a function of the number of LO4, modified sites. LO5 38 Michela Curradi et al. Mol. Cell. Biol. 2002;22:3157-3173  Methylation Process LO3 39 LO3, LO4, LO5 HISTONE Methylation Histone Methyltransferases add methyl groups to specific histone residues ◦ This correlates with changes in heterochromatin and euchromatin as well CHROMATIN REMODELING The molecular mechanism of chromatin remodeling frequently involve repositioning, acetylation, methylation, and/or replacement of histone variants Several different multi-protein complexes, known as chromatin-remodeling complexes (CRCs), can restructure chromatin to increase or decrease transcription CRCs use energy derived from ATP to initiate changes CRCs can disrupt nucleosome structure without displacing them or reposition the nucleosomes making key DNA-binding sites accessible LO1, Heterochromatin vs LO2, LO3 Euchromatin LO1, LO2, LO3, Euchromatin vs Heterochromatin LO4, LO5 42 LO1, LO2, LO3 Facultative Heterochromatin SILENCED euchromatin Deactivated by multiple processes ◦Changes in Methylation ◦Hypoacetylation ◦Changes in the timing of DNA replication Mono and Dimethylated H3-Lys9 LO1, LO2, LO3 Constitutive Heterochromatin DNA which is theoretically never transcribed but plays critical structural roles Highly repetitive sequences Significant percentage of human genome (15-20%) Trimethylated H3-Lys9  Chromatin Remodeling LO1, LO3, Complex: LO5 Activity and Consequences Remodeling does not solely have to be about heterochromatin and euchromatin transitions Shifting the material associated with nucleosomes can also influence gene expression even when not tightly coiled Chromatin Remodeling Complex: Activity and Consequenc es LO1, LO5 Importance of Heterochromatin Originally thought to be a repository of “junk” DNA Findings now indicate that is has structural and functional importance ◦ Believed to confer strength and protection to centromeres ◦ May protect against change in sequence; can prevent crossing over ◦ May aid in alignment and separation of chromosomes during mitosis and meiosis ◦ Heterochromatic regions of Y-chromosome have been shown to contain fertility factors ◦ Heterochromatin also serves to more “permanently” turn off genes that were used in development and are no longer needed ◦ Role in cellular specialization and differentiation LO1, LO3, LO5 Model for the molecular mechanisms of gene silencing mediated by DNA methylation. 49 Michela Curradi et al. Mol. Cell. Biol. 2002;22:3157-3173 LO1, LO6 Epigenetics and Imprinting Core phenotypic changes due to changes in gene expression WITHOUT changes in the core DNA sequence Differentially methylated domains of imprinted genes contain CpG-rich, imperfect tandem repeats resulting in a RELATED DNA STRUCTURE implicated in imprinting ◦ Specifically, the establishment and maintenance of parent of origin-specific methylation patterns PATERNALLY imprinted ◦ Paternal gene is OFF ◦ Maternal gene is ON MATERNALLY imprinted ◦ Maternal gene is OFF ◦ Paternal gene is ON LO1, LO6 Imprinting in Gametogenesis Original imprinting in the gamete is erased prior to spermatogenesis and oogenesis Selective silencing Different genes are silenced during oogenesis than spermatogenesis leading to specific maternal vs paternal imprinting patterns De-methylation and Re-methylation cycles to add and erase imprinting LO1, LO6 Imprinting in Gametogenesis Erasure via DEMETHYLATION (active or passive) Multiple mechanisms including deamination followed by repair and exclusion or regulation of key maintenance molecules like LO1, Differentially Methylated LO6 Regions and Disorders (23 DMRs exist) White circle = maternal differentially methylated regions Black circle = paternal differentially methylated regions BWS = Beckwith-Wiedemann Syndrome AS= Angelman Syndrome PWS= Prader-Willi Syndrome SRS= Silver-Russell Syndrome TNDM transient neonatal diabetes mellitus RB Retinoblastoma Important considerations for imprinting UPD14 uniparental disomy 14 in the use of assisted reproductive PHP1b pseudohypoparathyroidism type technologies https://www.ncbi.nlm.nih.gov/pmc/article 1b s/PMC4182590/pdf/RMB2-13-193.pdf LO1, LO7 X-Inactivation Introduction First described by Geneticist Mary Lyon Lyonization = X chromosome inactivation Necessary for maintaining the balance of X-linked genes Happens early in development during embryogenesis X-inactivation in human tissues is either RANDOM or imprinted Some genes on the inactive X (Xi) are still transcribed LO1, LO7 Effects of X-Inactivation Dosage Compensation ◦Total amount of gene product between males and females is made essentially equal Mosaicism ◦Different cells within an individual can have different chromosomal make-up Variable Expression ◦Females heterozygotes for disease alleles can have different or varying manifestations LO1, LO7 Structure of Inactive X Chromosome X-chromosome inactivation is a form of epigenetics Facultative Heterochromatin Hypermethylated and hypoacetylated histones 85% silenced with genes escaping inactivation primarily located on the short (p) arm Inactivated X’s pick up stain more due Inactive X = Barr Body to increased presence of methyl groups  Process of LO1, LO7 X- Inactivation Determine Number of Xs Choose extra X to inactivate Initiate Inactivation Expand/Spread the Inactivation Signal along appropriate regions of chromosome Maintain the inactivation LO1, LO7  Mosaicism LO1, LO7, LO8 Anhidrotic Ectodermal Dysplasia ◦ Patches of skin without sweat glands ◦ It is similar to the mosaicism observed with calico cats Other diseases are also observed to be mosaic due to random X-inactivation LO5, Summarizing Methylation and LO6, LO7 X-inactivation LO5, LO6, Errors in Heterochromatin LO7 Formation and/or Epigenetics and Human Disease Facioscapulohumeral muscular dystrophy ◦ Characterized by weakness and atrophy of particular muscle groups (predominantly face, shoulders, and upper arms) Friedreich’s ataxia ◦ Characterized by impaired or uncoordinated muscle movement Fragile X syndrome ◦ Characterized by developmental delays and learning difficulties ◦ Expansion of CGG sequence repeats in FMR1 gene ◦ More CGG = More Methylation Potential Prader-Willi Syndrome and Angelman Syndrome LO5, LO6, LO7 Disease Examples NOTE: These are not necessarily diseases of imprinting but rather diseases that differentially manifest due to patterns of imprinting MATERNALLY IMPRINTED PATERNALLY IMPRINTED Prader-Willi Syndrome ANGELMEN SYNDROME Maternal copy is OFF; Paternal is Paternal Copy is OFF; Maternal is deleted or lost or inappropriate pattern deleted, or lost or inappropriate pattern placed placed Loss of 15q11-13 Loss of 15q11-13 Gene Expression Lost = SNRPN and Gene Expression Lost = UBE3A NDN Developmental and intellectual Hypotonia, obesity, hypogonadism deficiencies, epilepsy and tremors LO5, Prader-Willi vs. Angelman LO6, LO7 Mitochondrial Genetics BMS 532 MOLECUL AR BIOLOGY AND GENETICS BLOCK 3 LECTURE 6 Objectives 1. Define the following terms: nucleoid, variable expression/variable patterns, parental leakage, and heteroplasmy 2. Explain the size and susceptibility to damage of the mitochondrial genome 3. Explain how inheritance of mitochondria differs from autosomal or sex- linked inheritance 4. List the different options for mitochondrial inheritance 5. Explain the role of mitochondrial DNA in human disease 6. Assess the inheritance of mitochondrial genomes based on the expected inheritance patterns and parental expression of the mitochondria LO1, LO2 Mitochondrial Genome (mtDNA) Circular genome (~16,500 base pairs) mtDNA is arranged with proteins into complexes = Nucleoids ◦ Contains all of the information for propagation, transcription, stabilization of the genome, and the small amount of repair they can perform ◦ Very limited repair abilities with high susceptibility to mutation (repair has evolved to deal with ROS but still limited) ◦ Mutations can occur in somatic cells and be propagated within a tissue causing accumulation of the altered mitochondria with aging Chinnery and Hudson LO1, LO3 More Mitochondrial Genetics Transcription and translation are possible within the mitochondria and resemble prokaryotic processes including polycistronic mRNA Variants of mitochondrial genomes have been identified via resequencing analyses Most humans actually contain multiple mitochondrial genotypes with specific patterns of variants accumulating in different tissues over time Mitotic events and the equal division of the cytoplasm mean that it is possible for a cell expressing multiple mitochondria to have offspring inheriting variable patterns of the mitochondria LO1, LO2, LO3, LO4 Mitochondrial Inheritance Most of the cytoplasm and therefore cytoplasmic material is contained within the oocyte thus mitochondria and their genomes are most often maternally inherited ◦ NOTE: Chloroplast inheritance is similar Inheritance patterns can vary among species ◦ Mammals = maternal inheritance ◦ Yeast (i.e. S. cerevisiae) = Biparental inheritance ◦ Plants (mitochondria AND chloroplasts) ◦ Angiosperms = most often maternal though biparental is possible ◦ Gymnosperms = usually paternal inheritance MOST offspring do NOT inherit any paternal mitochondria when maternal inheritance is expected Parental Leakage refers to the occasional inheritance of mitochondria via sperm when maternal inheritance is typical ◦ Mouse example = 1 to 4 per 100,000 mitochondria are inherited via paternal means LO1, LO2, LO3, LO5 Mitochondrial Inheritance Cannot use traditional Punnett squares to evaluate inheritance Must consider: 1) mode of inheritance (Maternal? Paternal? Biparetal?) 2) whether parent of origin has the ability to express more than one type ◦ Heteroplasmy = expressing mutations alongside normal counterparts ◦ More than one type of mitochondria present ◦ Variable proportions of mutant and wildtype versions are possible Also must consider the genotype to phenotype ratio Knorre 2019 LO1, LO2, LO3 Mitochondrial Inheritance In situations where more than one type of mitochondrion is observed, the inheritance of the mitochondria is more varied ◦ Example: If a plant has more than one chloroplast (one for green and one for white) and exhibits a mixed phenotype (both green and white) in their leaves ◦ the offspring could have white leaves, green leaves, or the mixture observed in the parent ◦ Tying this to mitochondria, if two types of mitochondria are present in the maternal parent ◦ the offspring could inherit one, the other, or both ◦ NOTE: some evidence in humans implicates familial specific biparental inheritance in humans (Luo et al 2018) though it could also be considered this variable inheritance from a maternal source with more than one mtDNA option LO1, LO5 Mitochondrial Disease and Inheritance There is a wide range of consequences and significant implications for mtDNA in human health Multiple tissues and organs can be affected by altered mitochondrial function ◦ Somatic mutations can lead to tissue specific consequences over time The complex inheritance patterns mean that there are different considerations for mtDNA disorders ◦ Maternal inheritance complicates female fertility for individuals with mitochondrial disorders Chinnery and Hudson LO6 Determining Inheritance Two individuals of a species have offspring. The maternal individual is heteroplastic while the paternal individual is homoplastic. Answer the following questions: ◦ If maternal mitochondrial inheritance is expected: ◦ What is the potential for the offspring? ◦ What is the potential for the next generation if the offspring are all female? All male? ◦ If paternal mitochondrial inheritance is expected: ◦ What is the potential for the offspring? ◦ What is the potential for the next generation if the offspring are all female? All male?