C4.3 - Human Genetics & DNA

Introduction

• Mendel’s Laws also apply to humans
• Inheritance in humans is a challenge to reconstruct
• Mutations in human DNA result in defective proteins
• Mutation may be
  • useful — positive mutation
  • harmful — negative mutation
  • with no effect — neutral mutation

The Genetic Material

deoxyribonucleic acid (DNA): molecule that composes genetic material

Packaging of DNA

• chromatin: mass of long fibers of DNA and protein (not usually visible w/ light microscope)
• chromosome: condensed DNA molecule that is visible under light microscope
  • 46 chromosomes in humans
  • 78 chromosomes in dogs
• DNA tightly coiled around proteins called histones
• The DNA and histone packages form structures resembling beads, called nucleosomes

Structure of DNA

• 1950s: Rosalind Franklin used X-ray crystallography to study DNA
• She found DNA had a helical shape
• Watson and Crick used her data to model DNA as a double helix
• Their model had sugar-phosphate backbones outside, nitrogenous bases inside

Components of Model

• DNA consists of long chain of subunits called nucleotides
• Parts of nucleotides
  • deoxyribose: ring-shaped sugar
  • phosphate group
  • nitrogenous base: single / double ring of carbon and nitrogen atoms
• 4 Types of Nucleotides
  • differ only in their nitrogenous bases
  • pyrimidines: single-ring structures
    • thymine (T) and cytosine (C)
  • purines: larger, double-ring structures
    • adenine (A) and guanine (G)
• Molecular arrangement
  • Nucleotides are linked by covalent bonds between sugar and phosphate
  • sugar-phosphate backbone: repeating pattern of sugar-phosphate
  • base pair: bonds between specific nucleotides to hold them together
    • complementary bases: nucleotides that hold each other
    • A pairs to T
    • C pairs to G
    • hold DNA together
    • causes the DNA to twist into a double helix
  • Knowing one strand’s sequence lets you determine the other
  • This explains how DNA is copied and passed on

DNA Sequences

• nucleotides can form countless sequences of varying lengths
• sequences store genetic information that codes for proteins and cell functions

DNA strand

Autosomal Recessive Inheritance

• autosomal recessive inheritance: recessive (masked) alleles carried on autosomes, not sex chromosomes
• autosomes: non-sex chromosomes, usually numbered
• harmful recessive mutations may persist masked by dominant trait
• i.e. Tay-Sachs disease
  • individuals lack lipid-degrading enzyme, fatal
• i.e. Albinism
  • eyes, skin, hair lack pigment melanin
  • individuals lack melanin-producing enzymes

Codominant Inheritance

codominant inheritance: form of inheritance where two different forms of an allele are expressed equally

Sickle-Cell Anemia

• individuals have hemoglobin defect
• hemoglobin: oxygen-carrying molecule in RBCs
• RBCs malformed and are prone to clogging capillaries starving tissues of oxygen
• HbA HbA: normal, RBCs often never sickle
• HbS HbS: severe, often fatal anemia, RBCs have sickle shape
• HbA HbS: no anemia; RBCs sickle only under low-oxygen conditions
• recessive gene may give heterozygous advantage to carriers
  • disorder found more frequently in African malarial zones

Autosomal Dominant Inheritance

• autosomal dominant inheritance: dominant alleles carried on autosomes
• result from chance mutations;
• or symptoms arise after child-bearing age
• i.e. Huntington’s Disease
  • deterioration of brain tissue
  • symptoms appear after age 35
  • genetic test available

Incomplete Dominance

• incomplete dominance: phenotype midway between dominant and recessive
• i.e. hypercholesterolemia
  • individuals lack LDL receptor protein
  • results in high cholesterol levels
• Incomplete Dominance = Codominance?

Sex-Linked Recessive Inheritance

• sex-linked recessive inheritance: recessive alleles carried over through sex chromosomes
• sex chromosomes: chromosomes that determine an individual’s sex
• first discovered by Morgan in fruit flies
• trait carried mostly on X chromosome, seldom on Y
• much more prevalent in male populations
• crosses can be visualized with Punnet squares

i.e. Colorblindness

Ishihara colorblind test

• affects 8% of men and 0.04% of women
• alleles for red and green found on X, but red is defective
• colorblind men cannot distinguish between red and green

i.e. Hemophilia

• hemophilia: blood clotting disorder
• individuals lack clotting factors
• 3 forms
  • A — Factor XIII
  • B — Factor IX
  • C — Factor XI
• mild cuts or bruises may lead to extreme joint pain or death
• treated w/ injection of clotting factors
• tainted blood scandal
• studied in pedigree of Queen Victoria’s family

Queen Victoria’s Family Tree

Genetic Testing

• carrier testing: test to determine if an individual carries a copy of a mutation that his / her children could inherit
• presymptomaticing: test that predicts the likelihood of developing a genetic condition
  • i.e. looking at family history
• diagnostic genetic testing: tests that confirms a diagnosis when symptoms for a particular genetic condition are present

Prenatal Testing

• human embryo becomes fetus ~7 weeks after fertilization
• prenatal testing: test that detects small-scale mutations or chromosomal alterations in a fetus
• conditions often screened for
  • spina bifida: birth defect involving incomplete development of spinal cord
    • may result in protrusion from opening in spine
  • Down syndrome
• amniocentesis: prenatal screening performed between 14th to 20th week of pregnancy (from textbook)
  • physician inserts needle into mother’s uterus
  • extracts some of amniotic fluid surrounding developing fetus
  • fetal cells tested for genetic disorders
• chorionic villus sampling (CVS): fetal testing of chorionic villi
  • chorionic villi: fingerlike projections that protrude from tissue surrounding fetus
  • physician extracts small sample of chorionic villi
  • by inserting narrow, flexible tube into mother’s uterus
  • conducted as early as 8th week of pregnancy
• Risks of Complication
  • maternal bleeding
  • miscarriage
  • premature birth
  • usually conducted only if there is high risk of genetic disorder

Newborn Screening

• newborn screening: testing a newborn infant for genetic disorders
• can detect some genetic disorders at birth through simple tests performed in hospitals
• screened for phenylketonuria (PKU)
  • inherited disorder
  • inability to break down naturally occurring amino acid phenylalanine
  • accumulation of phenylalanine may lead to severe developmental delays
  • diet low in phenylalanine usually sufficient to prevent onset of developmental delays