Basics of Genetics PDF

BASICS OF GENETICS Dr. Sim M. Simolde Assistant Professor COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO...

BASICS OF GENETICS Dr. Sim M. Simolde Assistant Professor COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 WHAT IS THE BRAIN OF THE CELL? P P P COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 CHROMOSOMES - Found in the nucleus of cells - Thread-like structures that carry genetic information from cell to cell. - Passed down from parents to their offspring 23 PAIRS OF CHROMOSOMES - 22 pairs of autosomes - 1 pair of sex chromosomes COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 CHROMOSOME PARTS: P arm - Short arm structure Q arm - Long arm structure COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 CHROMOSOME PARTS: Centromere - Constricted region that controls chromosome segregation at mitosis and meiosis Telomere - Region of repetitive DNA sequences at the end of a chromosome. - Prevent the ends of chromosomes from tangling COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 CHROMOSOME PARTS: COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 CHROMOSOME PARTS: 2 IDENTICAL CHROMATIDS - One is an exact copy of the other. - Formed during the synthesis (S) phase of the cell cycle - Each chromatid contains one DNA molecule COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 NUCLEOSOME 1. NUCLEIC ACID 2. HISTONES - Most abundant chromatin protein - Rich in arginine and lysine - Divided into two types Composed of pairs of H₂A, H₂B, H₃, H₄ Core histones They forma histone octamer H₁ is seen in the linker region Linker histones Loosey bound to the nucleosome COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 NUCLEIC ACIDS Are composed of: 1. SUGAR 2. NITROGENOUS BASE 3. PHOSPHATE COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 NUCLEIC ACIDS P O C5 SUGAR (Pentose) NB C1 Nitrogenous base C4 C1 C2 -H or -OH C3 -OH C4 C5 Phosphate -OHC3 C2 -H or -OH COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  NUCLEIC ACIDS PURINE NITROGENOUS BASE PURINE (Heterocyclic rings) PYRIMIDINE (Single ring) Adenine Cytosine Guanine Uracil (RNA) Thymine PYRIMIDINE PURE As Gold CUT the PY (pie) COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  NUCLEIC ACIDS PHOSPHATE GROUP - Negatively charged - Attached to C5 COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 NUCLEIC ACIDS SUGAR NITROGENOUS BASE PHOSPHATE PURINE/ PYRIMIDINE P H3PO4 Ribose Adenine Cytosine Deoxyribose Guanine Thymine NUCLEOSIDE COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  SUGAR NITROGENOUS BASE PHOSPHATE ADENINE THYMINE Ribose P H3PO4 GUANINE CYTOSINE Deoxyribose NUCLEOSIDE Ribose + Adenine = Adenosine Ribose + Guanine = Guanosine Deoxyribose + Thymine = Deoxythymidine COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 NUCLEIC ACIDS SUGAR NITROGENOUS BASE PHOSPHATE PURINE/ PYRIMIDINE P Ribose Adenine Cytosine Deoxyribose Guanine Thymine NUCLEOSIDE NUCLEOTIDE COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  SUGAR NITROGENOUS BASE PHOSPHATE Ribose Adenine P AMP OH P ADENOSINE ADP P ATP COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  BASE PENTOSE NUCLEOSIDE NUCLEOTIDE (+ 1 PO) Adenine Deoxyribose D-Adenosine D-Adenosine monophosphate Guanine Deoxyribose D-Guanosine D-Guanosine monophosphate Cytosine Deoxyribose D-Cytidine D-Cytidine monophosphate Thymine Deoxyribose D-Thymidine D-Thymidine monophosphate Adenine Ribose Adenosine Adenosine monophosphate Guanine Ribose Guanosine Guanosine monophosphate Cytosine Ribose Cytidine Cytidine monophosphate Uracil Ribose Uridine Uridine monophosphate COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 FUNCTIONS OF NUCLEOTIDES - Building blocks of nucleic acid Others: Carriers of activated intermediates of CHO, CHON, FATS Structural components of coenzymes Second messengers in signal transduction pathways Principal biologic transducer of free energy Regulatory compounds of pathways in intermediary metabolism Synthetic analogs are used as drugs What is the most abundant free nucleotide in mammalian cells? COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  COMPLEMENTARITY HYDROGEN BONDS - Weak electrostatic bonds A-T G- C 2-H bonds 3-H bonds COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 HYDROGEN BONDS - Denatured by extremes of heat, pH, and destabilizing agents Stable at pH 4-9 Disrupted by formamide - G-C base pairs require more energy to disrupts that A-T base pairs COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  ANTIPARALLEL 5 ARRANGEMENT 3 Sugar Phosphate backbone: Phosphodiester bonds 5 - Covalent bond formed by phosphorus and oxygen 3 atoms creating a stable linkage. 5 COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES 3 COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 Deoxyribonucleic acid (DNA) ❖ length of fully extended eukaryotic molecule is 3 m per genome ❖ contain the genetic information of an organism, packaged in chromatin using histones and organized into chromosomes ❖ located in the nucleus in eukaryotes and in the nucleoid region of the cytosol in prokaryotes COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 Ribonucleic acid (RNA) ❖ single stranded molecule ❖ ribose sugar containing a hydroxyl group at the 2' position ❖ thymine is replaced by the methylated uracil ❖ susceptible to alkaline hydrolysis ❖ rapidly degraded by RNA - specific enzymes COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 HOW MANY CHROMOSOMES? COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 HOW MANY CHROMOSOMES? COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  = 46 CHROMOSOMES = 46 CHROMATIN = 46 CHROMOSOMES = 92 CHROMATIN COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 WHEN ARE CHROMOSOMES VISUALIZED? COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  1.Nuclear membrane 2.Nucleoplasm 3. Nucleolus COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  EUCHROMATIN HETERO- CHROMATIN 1.Nuclear membrane 2.Nucleoplasm 3. Nucleolus COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  EUCHROMATIN HETERO- CHROMATIN 1.Nuclear membrane 2.Nucleoplasm 3. Nucleolus COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  HETEROCHROMATIN EUCHROMATIN - Tightly packed form of DNA - Loosely packed form of DNA - Stained dark - Lightly stained - High DNA density - Low DNA density - Transcriptionally inactive - Transcriptionally active - Peripherally located - Centrally located Fx: Maintains the structural Fx: Allows transcription of genes. integrity of the genome. COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  HETEROCHROMATIN EUCHROMATIN COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 WHEN ARE CHROMOSOMES VISUALIZED? COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 CELL CYCLE COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 CELL CYCLE COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 INTERPHASE - Interval between cell divisions - Chromatin: Relaxed - Divided into 3 phases Gap 1 (G1) Synthesis (S) Gap 2 (G2) DNA Replication - ↑ Metabolic activity - Cell differentiation 2n→ 4n COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 INTERPHASE - Interval between cell divisions - Chromatin: Relaxed - Divided into 3 phases Gap 1 (G1) Synthesis (S) Gap 2 (G2) Commit DNA Replication Cell Growth - Organelle production - ↑ Metabolic activity - ↑ volume - Protein synthesis - Cell differentiation - ↑ cytoplasm - DNA repair (Thymidine) 2n→ 4n G0 - Withdraw from cycle - Quiescence COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 TYPES OF SOMATIC CELLS LABILE CELLS STABLE CELLS PERMANENT CELLS - Regenerate regularly - Quiescent cells (G0) - Non proliferative - Cells continuously - ↓ proliferative activity - No division in lost and replaced - Divide in response to postnatal life injury - Surface epithelium - Parenchymal cells - Nerve cells - Mucosal epithelium Liver, kidney, lungs - Cardiac muscle cells - Hematopoietic cells - Endothelial cells - Fibroblasts COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  PROPHASE ≧ half of mitosis Key events: - Migration of two centrioles - Organization of microtubules - Nuclear envelope breakdown - Nucleolus disintegrates - Chromatin fibers condense COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  METAPHASE Migration of chromosomes to the equatorial plane/ metaphase plate Key events: - Binding of the spindle fibers to the chromosome kinetochore. - Degradation of cohesin by enzyme: separase - Sister chromatid arms disjoin, except at the centromere COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  METAPHASE Kinetochore - Protein within centromere where spindle fibers attach Cohesin - Holds sister chromatin together Shugoshin - Prevents cohesin from being degraded by separase COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  ANAPHASE Shortest stage of mitosis Disjunction of sister chromatids Key events: - Degradation of shugoshin - Sister chromatids of each chromosome are pulled toward the opposite poles of the cell COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  TELOPHASE Final stage of mitosis Key events: - Formation of cleavage furrow - Cytokinesis - Chromatin loosens COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 MEIOSIS - Reductional division - Produces gametes - Involves 2 successive cell divisions - Produces 4 haploid (n) daughter cells - Each daughter cell is genetically different COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 MEIOSIS Crossing over - Genetic exchange between a homologous pair of chromosomes COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 MEIOSIS COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  DNA REPAIR COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 DNA REPAIR COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  DNA LESION CAUSE REPAIR MECHANISM DISEASE Mismatched strand Errors that escaped Mismatch repair (MMR) Hereditary nonpolyposis proofreading colon cancer (Lynch syndrome) Pyrimidine dimers UV exposure Nucleotide excision repair Xeroderma pigmentosum (usually thymine) (NER) Base alterations Deaminating compounds Base excision repair (BER) MUTYH- associated (cytosine to uracil, or polyposis (MAP) Guanine to xanthine) Double strand breaks Ionizing radiation Non- homologous end Severe combined Free radicals joining (NHEJ) immunodeficiency Anti-tumor drugs (SCID) Homologous recombination (HR) COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 DNA REPAIR COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 MUTATIONS COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 MUTATIONS - Any permanent change in DNA base sequence - Physical, biochemical, or by mutagens - Potential to change the mRNA sequence & AA sequence MOST COMMON - Point mutations, frameshift mutations (insertion or deletion) OTHERS - Large segment deletion, Splice donor or acceptor, Triple repeat expansion COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 POINT MUTATION TRANSITION Purine to purine / Pyrimidine to pyrimidine TRANSVERSION Purine to pyrimidine or vice versa COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 POINT MUTATION 1. Silent mutation - A base change that doesn’t affect the amino acid sequence 2. Missense mutation - A base change that alters a protein’s amino acid 3. Nonsense mutation - A base change that causes a premature stop codon COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 FRAMESHIFT MUTATION - When a DNA sequence is altered by insertion or deletion of one or more nucleotides - *NOT a multiple of three COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 Gene - Functional unit of inheritance - Composed of a sequence of nucleotides - Codes for a product (RNA or protein) Locus - Position of a gene in a chromosome Allele - Alternative form of a gene in the same locus COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  Homozygous Heterozygous Genotype TT Tt Phenotype Tall Tall T is dominant t is recessive Homozygous - Alleles are the same (TT, tt) Heterozygous - Alleles are different (Tt) COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 MENDELIAN DISORDERS COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  AUTOSOMAL DOMINANT - One dominant allele is enough to produce phenotype - One parent is usually affected Father: affected (Hh) H h h Mother: Hh hh Unaffected (hh) h Hh hh COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 AUTOSOMAL DOMINANT SYSTEM DISORDER Nervous Huntington disease, Neurofibromatosis, Myotonic dystrophy, Tuberous sclerosis Urinary Polycystic kidney disease Gastrointestinal Familial polyposis coli Hematopoietic Hereditary spherocytosis, Von Willebrand disease Skeletal Marfan syndrome, Ehler- Danlos syndrome, Osteogenesis imperfecta Metabolic Familial hypercholesteolemia, Acute intermittent porphyria COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  AUTOSOMAL RECESSIVE - Two recessive alleles produce phenotype - 25% express disease, 50% carrier, 25% normal Father: carrier (Ss) S s Mother: carrier S SS Ss (Ss) s Ss ss COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 AUTOSOMAL RECESSIVE SYSTEM DISORDER Metabolic Cystic fibrosis, Phenylketonuria, Galactosemia, Homocystinuria, Wilson disease, Hemochromatosis Hematopoietic Sickle cell anemia, Thalassemia Endocrine Congenital adrenal hyperplasia Skeletal Ehler- Danlos syndrome, Alkaptonuria Nervous Neurogenic muscular atrophies, Friedrich ataxie, Spinal muscular atrophy COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973  X- LINKED DOMINANT (XD) A. In a cross of heterozygous female B. In a cross of affected male with with a normal male: a normal female 50% of sons and 100% of daughters with disease 50% of daughters with disease 0% of sons with disease -A- x y -B- X y X Xx Xy x Xx xy x xx xy x Xx xy COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 X LINKED DOMINANT SYSTEM DISORDER Metabolic Alport syndrome Skeletal Vitamin D- resistant rickets COLLEGE OF MEDICINE COLLEGE OF ALLIED MEDICAL SCIENCES CEBU DOCTORS’ UNIVERSITY PRIMUM HOMO ESTO 1973 X LINKED RECESSIVE (XR) - Usually males express phenotype (due to homozygosity for the allele) - Affected males do not transmit the disease to their sons , but all of their daughters are carriers - In a cross of heterozygous female and affected male: SONS: 50% (+) disease, 50% (-) disease DAUGHTERS: 50% (+) disease, 50% carrier -A- X Y -A- X Y x Xx xY X XX XY x Xx xy x Xx xy X LINKED RECESSIVE SYSTEM DISORDER Musculoskeletal Duchenne muscular dystrophy Hematopoietic Hemophilia A and B, Chronic granulomatous disease, G6PD deficiency Immune Agammaglobulinemia, Wiskott-Aldrich syndrome Metabolic Diabetes insipidus, Lesch Nyhan syndrome Nervous Fragile X syndrome