LIF111 Lecture 3: Mendelian Inheritance & Meiosis (Oct 2024) PDF

LIF111 Lecture 3: 04 October 2024 Mendelian inheritance and Meiosis https://vimeo.com/22416575 Meiosis and continuity of life: a Frank Gregorio movie ©2005 Lee Bardwell  New Topic Chromosomal basis of Mendel...

LIF111 Lecture 3: 04 October 2024 Mendelian inheritance and Meiosis https://vimeo.com/22416575 Meiosis and continuity of life: a Frank Gregorio movie ©2005 Lee Bardwell  New Topic Chromosomal basis of Mendelian inheritance Mendel explained inheritance in pea in 1865 – it was not called a law in those days – it was hardly noticed. The physical basis of Mendelian inheritance was clear when chromosomes were discovered and their transmission in somatic cells (by Mitosis) and Gametes (Meiosis) was understood in the early 1900s Summary of our current understanding  RECAP: The life cycle of a cell Cell cycle consists of 2 major phases – Interphase, where RECAP: chromosomes duplicate and cell parts are made – The mitotic phase, when nuclear division occurs  RECAP: INTERPHASE PROPHASE Centrosomes Early mitotic Centrosome Fragments Kinetochore (with centriole pairs) spindle of nuclear Chromatin envelope Centrosome Spindle Nucleolus Nuclear Plasma Chromosome, envelope membrane consisting of two microtubules sister chromatids Figure 8.6  RECAP: METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS Metaphase Cleavage Nucleolus plate furrow forming Spindle Daughter Nuclear chromosomes envelope forming Figure 8.6 (continued)  home: RECAP: DNA/Chromati n is seen in distinct physical forms at different stages of the cell cycle X chromosome DNA, Chromatin and Chromosome This is where we see chromosome as discrete entities under microscope  The confusing terminology of Mother Chromatid versus Chromosome cell When the cell divides, the Chromatid sister represents chromatids separate identical copies of a Chromosome duplication replicated chromosome that are held together at the centromere. These sister Sister chromatids chromatids are derived from the same mother Daughter chromosome. These are cells again called chromosomes when sperate during nuclear Chromosome – Two daughter division cells are distribution to produced daughter cells – Each has a complete and identical set of  Meiosis – A process to generate haploid sets of chromosomes Gamete carry haploid set of chromosomes  MITOSIS MEIOSIS MITOSIS PARENT CELL MEIOSIS (before chromosome replication) Site of crossing over PROPHASE PROPHASE I Tetrad formed Duplicated Chromosome Chromosome by synapsis of chromosome replication replication homologous (two sister chromatids) 2n = 4 chromosomes Chromosomes Tetrads METAPHASE align at the align at the METAPHASE I metaphase plate Metaphase plate ANAPHASE Homologous ANAPHASE I Sister chromatids TELOPHASE chromosomes TELOPHASE I separate during anaphase separate during anaphase I; Haploid sister n=2 chromatids Daughter remain together cells of meiosis I 2n 2n No further chromosomal MEIOSIS II Daughter cells replication; sister of mitosis chromatids separate during anaphase II n n n n Daughter cells of meiosis II  MEIOSIS I: Homologous chromosomes separate INTERPHASE PROPHASE I METAPHASE I ANAPHASE I Centrosomes Microtubules Sites of crossing over Metaphase Sister chromatids (with attached to plate remain attached centriole Spindle kinetochore pairs) Nuclear Chromatin Sister Tetrad Centromere Homologous envelope chromatids (with kinetochore) chromosomes separate Note the separation of paired chromosomes and NOT that of chromatids  MEIOSIS II: Sister chromatids separate TELOPHASE I TELOPHASE II PROPHASE II METAPHASE II ANAPHASE II AND CYTOKINESIS AND CYTOKINESIS Cleavage furrow Sister Haploid chromatids daughter cells separate forming This time Figure 8.14, part 2 chromatids separate  Gametes have a single set of chromosomes Haploid gametes are produced by a special sort of cell division called meiosis Which occurs only in reproductive organs, ovaries and testes Purpose of meiosis is to produce sperm and egg and reduce the diploid set of chromosomes to a haploid set  MEIOSIS Hallmarks Meiosis involves 2 cell divisions Meiosis produces 4 cells from 1 parental cell Each of the 4 daughter cells has 23 individual chromosomes rather than 23 pairs of chromosomes Meiosis reduces the chromosome number from diploid to haploid Meiosis, like mitosis, is preceded by chromosome duplication – However, in meiosis the cell divides twice to form four daughter cells  Are these duplicated? Meaning already replicated What replicates? Chromosome, DNA or both?  Food for your thought What makes genetic inheritance a full-proof mechanism?   Which one is a chromosome and where are the chromatid?  How do we count chromosome number?  How many ‘sets’ of chromosomes are seen here?  Idea of diploid ‘2n’ and haploid ‘n’ sets A karyotype (ORDERED ARRANGEMENT) of metaphase chromosomes ( in homologous pairs)  Goals of Pedigree Analysis  Determine the mode of inheritance: dominant, recessive, partial dominance, sex-linked, autosomal etc.  Determine the probability of an affected offspring for a given cross. Symbols used in pedigree analysis: Male Sex unspecified Female Affected Mating individuals Heterozygotes Parents & for autosomal Children: recessive 1 boy; 1 Carrier of sex girl linked recessive (in order of birth) Death Dizygotic (non Abortion or identical still birth Twins) Propositus Monozygotic (identical Twins) Consanguineous marriage  Pedigree Analysis Marriage Normal female Normal male I One these parent was therefore a carrier 1st born II Affected Siblings Is the mutant allele dominant or recessive? Pedigree Analysis  A Pedigree Ww ww I 1 2 II 1 2 ww 3 ww 4 5 Ww 6 Ww ww Ww III 1 2 3 4 5 6 7 8 9 10 ww ww ww Ww ww ww Ww Ww ww Ww  Sex-linked inheritance The inheritance of genes located on the sex chromosome  Autosomal vs. sex-linked traits  Autosomal traits are caused by genes on autosomes (chromosome 1-22) – autosomal recessive or dominant traits /diseases  Sex-linked traits are caused by genes on the sex chromosomes (X or Y) – X-linked recessive or dominant traits /diseases  Albinism : Autosomal recessive inheritance Why this inheritance is called autosomal?  Achondroplasia: Autosomal dominant inheritence Why this called autosomal dominant dominant ? Sex Determination in humans Parents  In such an inheritance Father pattern what is the ready XAY sign of sex- linkage? XA Y Daughter Son X XXA XY affected normal Mother XX Daughter Son X XXA XY affected normal X-linked dominant  X-linked recessive disease Female carrier* mates with normal male Sperm FxM XN Y X NX A X NY XN F M X NX N X NY normal normal Eggs XA F M XA XN XA Y carrier affected Half* her daughters will be carriers Half* her sons will be affected *a statistical probabilty X-linked recessive disease Affected male mates with normal female Sperm FxM XNXN XAY XA Y XN F M XNXA XNY carrier normal Eggs XN F M XNXA XNY carrier normal All his daughters will be carriers None of his sons will be affected Pedigree Illustrating Inheritance Pattern of an X-Linked dominant mutation  Pedigree Illustrating X-Linked Recessive Inheritance Pattern Great grand mother Grand mother Nani Grand Uncle Grand daughter Uncle (mama) Nephew Hemophilia : X-linked recessive Empress of India 1876 Queen Victoria (1819-1901) passed haemophilia A on to many of her descendants  Hemophilia: The Royal Disease The inheritance of the X-linked recessive condition hemophilia in the royal families of Europe  Edward Victoria (Duke of Kent) (Princess of Saxe-Coburg) Victoria Albert (Queen of England) Arthur Victoria Frederick Alice Louis Alfred Helena Louise Leopold Helen Beatrice Henry Wihelm II Sophie George V Alix Nikolas II of Russia Alfonso XII Spain Eugenic George VI Waldemar Henry Alexic Alfonso Gonzal o Queen Prince Philip Elizabeth Normal Male Normal Female Hemophilic Male Pedigree chart of X-linked hemophilia in the royal Carrier Female families of Europe ? Male died in infancy Possible hemophilic Some X-linked recessive human diseases Hemophilia A Hemophilia B Red-green color blindness Duchenne muscular dystrophy Retinitis pigmentosum (one of many loci) Lesch-Nyhan Syndrome Many others Some X-linked dominant human diseases Incontinentia Pigmenti Hypophosphatemic Rickets Charcot-Marie-Tooth disease Chondrodysplasia Punctata  Hypertrichosis pinnae auris : Y-linked XY X X X XY X X XY XY X X X X X X X XY XY X X As only males have a Y chromosome, the genes are simply passed from father to son. Every son of the father will be affected. Very few Y-linked disorders are know except infertility Problems and examples of chromosomal inheritance nheritance of eye coloration in fruit fly, Drosophila: An example of sex-linked inheritance Normal Red Mutant white  First : Observe No eye coloration : white eyed Normal eye coloration : red How do we name the gene and what are eyed its alleles?? Gene name white Normal Allele : white (+) red pigmentation Mutant allele : white no pigmentation Which one is recessive and which one is dominant?  Then test and infer w+w+ ww W+ W 43 w+w w+w w+w w  Problem A yellow body-colored female fruit fly was mated to a male with normal body color (brown). All the female progeny were brown (normal) while all the male progeny were yellow. What does this inheritance pattern signify? Solve this problem Significance of chromosome numbers in in heritance  What if individual chromosomes do not separate during meiosis? Error in chromosome number  The Culprit: Non-disjunction Older women are more likely than younger women to evidence chromosome damage and meiotic irregularities Pre-natal Diagnosis: Amniocentesis Will it be possible to detect a defective gene by amniocentesis? Fetal cells present in amniotic fluid are then cultured and analyzed for chromosomes (karyotyping) and other biochemical tests  This baby has one X chromosome. Yet it is a female baby. Why? Monosomy: Turner’s Syndrome: 44+X  Individual chromosome segregation going wrong during meiosis Why down’s syndrome does How can errors not suggest in abnormal sex chromosomal linked inheritance? segregation result in Down’s syndrome? Trisomy of chromosome. 21: Down’s Syndrome: 45+XY/45+XX Other disorders: Trisomy-13 (47:+13), Trisomy-18 (47:+18), Klinefelter Syndrome (44+XXY), Triple X syndrome (44+XXX), XYY trisomy (44+XYY) People suffering from Down syndrome can lead a reasonably normal life  A home-work Which neurodegenerative disease Stephen Hawkins suffered from? Is that disease genetic? Why Stephan Hawkins’ condition could not be treated?