Presentation on theme: "Make a Life to Save a Life"— Presentation transcript:
1Make a Life to Save a Life byPeggy BrickmanUniversity of Georgia
2The CaseJack and Lisa Nash’s daughter Molly was born with a rare, incurable genetic condition called Fanconi anemia, which rendered her body unable to produce enough blood cells…
3Matching Organs: HLAFinding a correct match for tissue transplantation depends on matching a specific group of proteins found on the surface of white blood cells that are used to distinguish one’s own cells from foreign cells, called HLA, for human leukocyte antigen.3
4Learning ObjectivesRecognize how the number and type of chromosomes differ in a gamete compared to a somatic (body) cell.Describe how chromosomes are separated in meiosis and how this differs from mitosis.Apply the knowledge of how chromosomes separate during meiosis and the rules of probability to predict the likelihood that offspring from two parents would inherit a specific combination of chromosomes and the genes they contain.
5Matches for Organ Donation HLA proteins encoded by several genes on chromosome 6.Many variants of gene = mutations that create differences (alleles)HLA Class IGeneABCEFGAlleles6971,10938192136HLA Class II1,0126
8Review: Mitosis Asexual reproduction. Occurs in somatic (body cells) Sister chromatidsA1A2B35B44Review: MitosisS phaseSister chromatidsAsexual reproduction.Occurs in somatic (body cells)for growth and division.Creates genetically identical cells.Not a way to combine traitstogether in reproduction.Need new method: sexual reproduction.A1A1B35B35A2A2B44B44mitosisA1A2A1A2B35B44B35B44
9Why do diploid organisms need to have specialized sex cells? Sex cells (gametes) allow traits to be combined from two organisms.Can’t just fuse any two random cells.2n (46)2n (46)+A1A2A3A26B35B44B41B354n = 92too many
10Sexual ReproductionMeiosis = specialized cell division so you have only one of each chromosome, calledGametes: (n) made only in gonad (testis, ovary)A2n (23)n (23)+A26B35B44A2A262n = 46B44B35
11Mitosis versus Meiosis DiploidsomaticcellgameteprecursorMITOSISdivisionduplicationDiploidHaploiddivisionMeiosis has 2 divisions: Meiosis I and Meiosis II
12CQ#1: When Mrs. Nash produces eggs, they would have which combinations of the HLA-A and HLA-B genes and in what proportions?100% B35-A150% B35-B44 & 50% A1-A250% B35-A1 & 50% B44-A2100% B44-A250% B35-A2, & 50% B44-A1B35A1B44A2Mrs. Nash’s chromosome 6s
14Chromosome Pairing: Synapsis Close proximity favors crossing overAllows exchange of traitsExchange of parts of non-sister chromatidsDuplicatedMaternalchromosomeDuplicatedPaternalchromosometetradsisterchromatidsnon-sisterchromatids
15Mitosis Meiosis I Homologues Pair mitosis meiosis I Sister chromatids B35B44B35B44Sister chromatidsSister chromatidsMitosisMeiosis IA1A1B35B35Homologues PairB35A1B44A2A2A2B44B44mitosismeiosis IA1A2A1A2A1A1A2A2B44B44B35B44B35B44B35B35
16Update: Meiosis I completed Homologous chromosomes are separated into two different cells.Each new cell has only one of each different chromosome (n, haploid).Still need to separate the sister chromatids so that the total amount of chromosomes and DNA is truly half of a normal cell.
17Meiosis II: Sister chromatids separate B44B44B35B35meiosis IIA1A1A2A2B35B35B44B44End result: Four haploid cells total
18CQ#2: When Mr. Nash produces sperm, the sperm would have which combinations of the HLA-A and HLA-B genes and in what proportions?100% B5-A2650% B35-A3 & 50% B41-A2650% B35-B41 & 50% A3-A26100% B44-A2 B35-A2650% B35-A26, & 50% B41-A3A3A26B41B35Mr. Nash’s chromosome 6s
19CQ#3: Which of the following shows one combination of HLA-A and HLA-B genes expected in an offspring of Lisa and Jack Nash?B35, B35, A1, A2B35, B44, A2, A3B44, B35, A2, A26B41, B44, A26, A2B35A1B44A2A3A26B41B35Mrs. NashMr. Nash
20CQ#4: Is it possible for any child born to this couple to be identical in both HLA-A and HLA-B with either parent?B35A1B44A2YesNoA3A26B41B35Mrs. NashMr. Nash
21CQ#5: Using the proportion of each type of sperm and egg that you calculated in questions I and II, what is the likelihood that Molly’s sibling would inherit the same combination of HLA genes and thus be a good organ donor for Molly?No chance25%50%75%100%Chromosome 6s for Molly NashA2A26B44B35
22Clearly Molly’s best chance of finding a bone marrow match was with a sibling. Unfortunately, Molly was an only child. The Nashes had always wanted to have more children, but because Fanconi anemia is an inherited condition, they knew that if they had another child that child had a chance of getting the disease just as Molly had. But neither Jack nor Lisa had the disease because the mutation is recessive. In order to have Fanconi anemia like Molly, both copies of the FANCC gene would have to have this recessive mutation, and they only had one. How is that possible?
24CQ#6: Using what you know about how meiosis created eggs and sperm, what is the likelihood that Lisa and Jack Nash could conceive a sibling for Molly that would NOT have Fanconi anemia (presence of at least one normal)?0%25%50%75%100%
25Punnett Squares: Show All Possible Combinations of Gametes NormalFANCCFatherNormalFANCCmeiosisFANCCnormalNormalFANCCmeiosisNormalFANCCMother
26Pre-Implantation Genetic Screening When they discovered that they could conceive a baby that was free from Fanconi Anemia, Jack and Lisa Nash underwent in-vitro fertilization followed by a procedure called pre-implantation genetic screening to choose an embryo that would have HLA proteins (B44, B35, A2, A26) that matched Molly, and to choose an embryo that would also be free of Fanconi anemia.
27Pre-Implantation Genetic Screening Ethics: This is the first example of the use of pre-implantation genetic screening to select for a baby solely as a treatment for its sibling.List two ethical objections someone might have to allowing the Nashes to use this technique.List two reasons why you think the Nashes should be allowed to use this technique.What kind of regulations if any should be used for parents hiring doctors to do this procedure? When is it OK, when not?
28Select a Baby: HLA Match, Normal FANCCB35B44A1A2NormalFANCCB41A3B35A26MotherFatherA2A26B44B35FANCCMolly
29CQ#7: Using your knowledge of how chromosomes segregate during meiosis, what percent of Mrs.Nash’s eggs would carry a normal chromosome 9 and a chromosome6 with the A-2, B-44 alleles?NormalFANCCB35B44A1A2No chance25%50%75%100%
30Alignment at Metaphase I Random: NormalFANCCB35B44A1A2NormalFANCCB35B44A1A2Meiosis IMeiosis IIMeiosis IMeiosis IIB35A1B44A2A1B35A2B44
31CQ#8: If the same percentage of Mr CQ#8: If the same percentage of Mr. Nash’s sperm carry the correct chromosome 9 (normal) and 6 (A26, B35), what is the probability that a single embryo would be a perfect HLA match for Molly and not develop Fanconi anemia?1/21/43/161/81/16NormalFANCCB35B44A1A2NormalFANCCB41A3B35A26Father
33Update on the NashesAfter four in vitro fertilization attempts, Lisa Nash gave birth to a baby boy, Adam, on August 29, Adam’s placenta was gathered immediately and all the cord blood saved. Molly started chemotherapy to destroy her bone marrow and received a transfusion of the cord blood cells a month later. Today Molly, Adam, and new little sister Delaine are all doing well. The transplant cured Molly’s bone marrow failure, but she still suffers from Fanconianemia and visits the doctors times a year to screen for solid-tumor cancers. A common cold could have dire consequences for her, but her bone marrow is functioning normally.
35Slide 5 —Bottom leftDescription: Drawing depicting HLA genes on chromosome 6.Author: Philip DeitikerSource: Wikimedia Commons,Clearance: Released into the public domain by the author.Slide 9 and Slide 10Description: Figure of male and female.Author: Derived from a public domain NASA image.Source: WikiMedia,Clearance: Public domain.All remaining images appearing in this presentation were created by the author of this case study, Peggy Brickman.