Genetic Control of Cell Function and Inheritance NUR 304 Dr. Dory Roedel Ferraro

It’s All in the DNA DNA (deoxyribonucleic acid) – extremely stable macromolecule Contains within its structure the basic information needed to: – Direct the function of our cells – Influence our appearance – Influence how we respond to our environment – Serve as a unit of inheritance that is passed on from generation to generation

DNA Long, double-stranded helical structure composed of nucleotides, which consist of phosphoric acid, deoxyribose, and one of four nitrogenous bases (T,C,A or G) Spiral staircase with paired bases representing the steps Nitrogenous bases carry the genetic information – Thymine (T) – Cytosine (C) – Adenine (A) – Guanine (G) Precise complimentary pairing of purine and pyrimidine – A is paired with T – G is paired with C

Replicating DNA Helix

DNA Each nucleotide in a pair is on one strand of the DNA molecule Bases on opposite DNA strands are bound together by hydrogen bonds Double-stranded structure of DNA molecules allows them to replicate precisely by separation of the two strands, followed by synthesis of two new complimentary strands Only one strand is used in transcribing Both strands are involved in DNA duplication

Chromosomes Discrete bundles of DNA containing genetic information Arranged in pairs; one from the mother and one from the father Humans have 23 pairs of chromosomes 22 are autosomes (have same appearance in males and females) 23 rd pair are the sex chromosomes (determine the sex of an individual) – Males have an x and y – Females have two x chromosomes

Patterns of Inheritance Genotype- total sum of the genetic information that is stored in the genetic code of a person Phenotype- represents the recognizable traits, physical and biochemical, associated with the genotype Expressivity- refers to the expression of a gene in the phenotype Penetrance- the ability of a gene to express its function Gene locus- the point on the DNA molecule that controls the inheritance of a particular trait

Patterns of Inheritance Alleles- alternate forms of a gene (one from each parent) Locus- the position they occupy on the chromosome Alleles at a gene locus may carry recessive or dominant traits Mendelian (single-gene) patterns of inheritance include autosomal dominant and recessive traits that are transmitted from parents to their offspring in a predictable manner

Patterns of Inheritance Recessive trait is one expressed only when two copies (homozygous) of the recessive alleles are present Dominant trait are expressed with either homozygous or heterozygous pairing of alleles Dominant traits are labeled with caps (D) Recessive with lower case (d)

Punnett Square

Autosomal Dominant Disorders Single mutant gene from an affected parent is transmitted to an offspring regardless of sex The affected parent has a 50% chance of transmitting the disorder to each offspring Unaffected siblings of the offspring do not transmit the disorder In some cases, the person with an autosomal dominant trait does not have an affected parent, but rather it is owed to a mutation involving either the sperm or the ovum

Autosomal Dominant Disorder: Marfan Syndrome Mutation of gene on chromosome 15 Prevalence is 1 in 20,000 Involves CV, skeletal and ocular systems Wide range of variation in the expression of the disease May have abnormalities of one or all three systems

Autosomal Dominant Disorder: Neurofibromatosis Neurogenic tumors that arise form Schwann cells Type 1 is relatively common (1 in 3500) and involves multiple neural tumors Type 2 tumors of the acoustic nerve

Autosomal Recessive Disorder Manifested only when both members of the gene pair are affected Both parents may be unaffected but are carriers of the defective gene Affect both sexes Tay-Sachs, Phenylketonuria are autosomal recessive disorders Occurrences – One in four for affected child – Two in four for a carrier child – One in four for a normal child (unaffected, non-carrier)

Chromosomal Disorder: Down Syndrome Most cases are caused by nondisjunction or an error in cell division during meiosis, resulting on a trisomy of chromosome 21 Risk of having a child with Down Syndrome increases with age Condition usually apparent at birth Increased risk of childhood leukemia Increased risk of Alzheimer’s disease

Maternal Age and Risk of Down Syndrome

Turner Syndrome An absence of all or part of one of a female’s X chromosomes Affects 1 in 5000 births Short stature with normal body proportions Diagnosis often delayed until late childhood or early adolescence Early diagnosis is an important aspect of treatment allowing for counseling and screening for cardiac, renal, thyroid and other abnormalities

Klinefelter Syndrome 47, XXY male Testicular dysgenesis accompanied by the presence of one or more extra X chromosomes 1 in occurrence Congenital hypogonadism May have a voice that is high- pitched, sparse beard and pubic hair, female fat distribution Infertility is common

Disorders Due to Environmental Influence Physiologic status of the mother – General state of health (DM associated with congenital defects) – Hormone balance – Nutritional status – Medications she takes Smoking Alcohol Infectious agents

Teratogenic Agents Radiation (microcephaly, skeletal malformations, intellectual disability) Environmental chemicals (mercury) Medications and illicit drugs Alcohol Infectious agents Nutrient deficiencies

Medications and Illicit Drugs Many drugs can cross the placenta Lipid soluble drugs cross more readily and enter the fetal circulation Determining factors – Rate at which a drug crosses the placenta – Duration of exposure – Stage of placental and fetal development at the time of exposure – Molecular weight of the drug (< 500 can cross easily)

Sensitivity of Specific Organs

Teratogenic Drugs Thalidomide Antimetabolites used in the treatment of cancer Anticonvulsants Warfarin Alcohol Cocaine

Alcohol Variable effects on fetal development ranging from minor abnormalities to fetal alcohol syndrome (FAS) Prenatal or postnatal growth retardation CNS involvement: neurologic abnormalities, developmental delays, skull and brain malformation, characteristic facial features

Clinical Features of Fetal Alcohol Syndrome

Infectious Agents Many microorganisms cross the placenta TORCH T=toxoplasmosis (animal excrement) O=other (varicella zoster, Epstein-Barre, syphilis) R=rubella C=cytomegalovirus H=herpes simplex type 2

Prenatal Screening and Diagnosis Ultrasonography Maternal serum markers Non-invasive prenatal testing (NIPT) Amniocentesis Chorionic villous sampling Percutaneous umbilical cord sampling