Genes and Genetic Diseases

1. Genes & Genetic Disease
Touro University Nevada
Patricia Strobehn, MSN, APRN, FNP-BC
Assistant Professor, School of Nursing

2. History of Genetics
• Gregor Mendel was the founder of Modern Genetics
• Discovered that chromosomes contain genes
• Humans have between 20,000-25,000 genes
• 1/3 of inpatient pediatric patients are children with genetic
disease

3. DNA Overview
• Double Helix is made of 4 nitrogenous bases – A,C,G,T
• Adenine, Cystosine, Guanine, Thymine
• Each DNA sub-unit is called a nucleotide
• DNA provides a code for the body’s proteins
• These Proteins form polypeptides
• Polypeptides are made out of the 20 possible amino acids
• The sequence of three bases are called Codons
• DNA is formed and replicated in the cell nucleus

4. Replication
• The DNA strand is untwisted and unzipped, the single
strand acts a template for replication.
• DNA must be able to replicate itself accurately during cell
division or mutations can occur.
• DNA polymerase pairs the complimentary bases together
• Accurate replication is the consistent pairing of A,C,G,T
• Complementary base pairing is the key to accurate
replication.
• Alterations in DNA sequencing can lead to disease

5. Replication

6. Replication Q & A
Which information is correct regarding DNA polymerase?
DNA polymerase functions to:
1. Signal the end of a gene.
2. Pull apart a portion of a DNA strand.
3. Add the correct nucleotides to a DNA strand.
4. Provide a template for the sequence of mRNA nucleotides.

7. Gene Mutation
• A mutation is an inherited alteration of genetic material.
• Usually a result of inaccurate replication
• Common types of Gene Mutations include:
Base Pair Substitution
Frame-shift Mutation
• Mutagens also alter DNA
• https://www.youtube.com/watch?v=eDbK0cxKKsk

8. Transcription
• Transcription is the process by which RNA is synthesized
from a DNA template.
• RNA is synthesized from the DNA template via RNA
polymerase.
• RNA polymerase binds to the promoter site on DNA.
• DNA specifies a sequence of mRNA.
• Transcription continues until the termination sequence is
reached.
• mRNA then moves out of the nucleus and into the
cytoplasm.
• Gene splicing occurs.
• Introns and extrons

9. Transcription

10. Translation
• Is the process by which RNA directs the synthesis of
a polypeptide via the interaction with transfer RNA
(tRNA).
• tRNA contains a sequence of nucleotides (anticodon)
complementary to the triad of nucleotides on the
mRNA strand (codon).
• Ribosome is the site of protein synthesis.
• Ribosome helps mRNA and tRNA make polypeptides.
• When ribosome arrives at a termination signal on the
mRNA sequence, translation and polypeptide formation
cease.

11. Translation Q & A
At what site does protein synthesis occur?
The site of protein synthesis is the:
1. Codon
2. Intron
3. Ribosome
4. Anticodon

12. Chromosomes
• Somatic cells
• Contain 46 chromosomes (23 pairs)
• One member from the mother; one from the father
• Diploid cells
• Gametes
• Sperm and egg cells
• Contain 23 chromosomes
• Haploid cells
• One member of each chromosome pair
• Meiosis
• Formation of haploid cells from diploid cells

13. Chromosomes
• Autosomes
• Are the first 22 of the 23 pairs of chromosomes in males and
females.
• The two members are virtually identical and are thus said to be
homologous.
• Sex chromosomes
• Make up the remaining pair of chromosomes.
• In females, it is a homologous pair (XX).
• In males, it is a nonhomologous pair (XY).
• Karyotype
• The length and centromere location determine the ordered
display of chromosomes.

14. Chromosomal Abnormalities
• Effects may or may not have serious consequences.
• Chromosome breakage
• If a chromosome break occurs, then the break is usually repaired
with no damage.
• Breaks can stay or can heal in a way that alters the structure of
the chromosome.
• Can occur spontaneously.
• Agents of chromosome breakage include Ionizing radiation,
chemicals, and viruses.

15. Chromosomal Abnormalities
• Deletions
• Chromosome breakage or loss of DNA
• Example: Cri du chat syndrome or “cry of the cat”
• Low birth weight, mentally challenged, and microcephaly
• Duplications
• Excess genetic material
• Usually have less serious consequences
• Inversion
• Chromosomal rearrangement in which a chromosome
segment is inverted: ABCDEFG becomes ABEDCFG
• Usually affects offspring

16. Chromosomal Abnormalities
• Translocation
• Is the interchange of genetic material between
nonhomologous chromosomes.
• Types of translocation
• Robertsonian: Long arms of two nonhomologous
chromosomes fuse at the centromere, forming a single
chromosome; is common in Downs syndrome.
• Reciprocal: Breaks take place in two different
chromosomes, and the material is exchanged
• Fragile Sites
• Chromosomes develop breaks and gaps

17. Genetic Transmission
• Humans are diploid organisms
• Chromosomal pairs are made from both Paternal and
Maternal DNA – XX XY
• Homozygous pairs- Identical genes
• Heterozygous pairs – Non- identical genes
• Genotype - The composition of genes at a specific location
• Phenotype - The outward appearance of an individual is a
result of both: the persons genotype and the environment.
• Dominant - The allele whose effects are observable
• Recessive – The allele whose effects are hidden
• Carrier – is an individual who has a disease-causing allele but
is phenotypically normal.

18. Autosomal Inheritance
Dominant
• Rare: Observed in less
than 1:500
• Does not skip
generations
• One parent has the
Phenotype
• Ex: Achondroplasia
Recessive
• Carriers are typically
phenotypically normal
• Can skip generations
• Requires a homozygous
recessive allele to
actually be expressed
• EX. Cystic Fibrosis

19. X- Linked Inheritance
• Y chromosome only contains a few dozen genes.
• Most of the sex-linked traits are located on the X-
Chromosome
• X-linked recessive diseases are much more common
• Females receive two long x-linked chromosomes and Males
receive one long x-linked chromosome and one short y.
• Males are more frequently affected

20. Multifactorial Inheritance
• Multifactorial Trait -Traits or disease in which variation is
thought to be caused by the combined effects of multiple
genes.
• Ex: Height: Phenotype is determined by genotype. >100 genes
have been identified to contribute to height.
• Ex: Blood Pressure: Phenotype is determined by genotype and
other environmental factors such as diet, exercise and stress.
• Twin Studies vs Adoption Studies

21. Multifactorial Disorders
• Coronary Heart Disease
• Accounts for 25% of all deaths in the U.S.
• Caused by Atherosclerosis
• Risk Factors: obesity, smoking, HTN, elevated cholesterol levels
and a family history
• An individual with a positive family history is 2-7x more likely to
have heart disease
• Risk increases with more affected family members
• Risk increases to 13x more likely if two first-degree relatives were
affected by CHD before the age of 55
• Women do develop at a later age than men

22. Multifactorial Disorders
• Familial Hypercholesterolemia (FH)
• LDL Receptor gene was discovered in 1894
• FH is caused by a reduced number of functional LDL receptors
• Autosomal Dominant FH accounts for 5% of Myocardial
Infarctions in individuals <60 years old.
• Heterozygotes: 1:500 individuals have cholesterol levels that are
usually twice the normal range.
• Homozygotes: 1:1,000,000 have cholesterol levels that range
from 600-1,200. Most experience MI’s before age 20.
• Individuals develop Xanthomas (fatty deposits) due to excess
levels of circulating cholesterol.

23. Multifactorial Disorders
• Breast Cancer
• Affects 12% of women by age 85 years old
• Risk doubles with one affected first-degree relative
• Autosomal Dominant individuals account for 5% of all breast CA
• BRCA1 and BRCA2 female carriers have a 50-80% overall lifetime risk
• BRCA2 male carriers have a 6% overall lifetime risk (100x other men)
• Colorectal Cancer
• Second leading cause of Cancer in the U.S.
• 1:20 Americans will be affected
• Risk is 2-3x more with one affected first-degree relative

24. Multifactorial Disorders
• Diabetes Mellitus
• Siblings of those with DM have a higher rate of susceptibility
• TCF7L2 gene has the most significance in regards to Type 2
• Most common risk factors for Type 2 are family history and
obesity
• Obesity
• Strong evidence exists for both heredity and environmental risk
factors
• Four adoption studies showed that body weights of adopted
individuals correlated significantly with their natural parent’s
body weights and not with their adoptive parent’s body weights.

25. Multifactorial Disorders
• Alzheimer Disease
• Risk doubles in those who have an affected first-degree relative
• Most cases do not appear to be caused by any single-loci
• Early onset occurs before age 65
• Early onset attributed to mutations in amyloid-beta precursor protein
(APP), presenilin 1 (PS1) and presenilin 2 (PS2)
• Common late onset occurs after age 65
• Later onset attributed to allelic variation of apolipoprotein E (APOE)
• Europeans and Japanese are at other risk than other populations

26. Multifactorial Disorders
• Alcoholism
• 10% of adult Males are affected
• 3-5% of Females are affected
• Risk of developing alcoholism of those with one affected parent is 3-5x
higher than those whose parents are unaffected
• Monozygotic twin studies have a concordance rate >60%
• Adoptive studies show that the offspring of an alcoholic parent, even
when raised by non-alcoholic parents have 4x the chance of developing
alcoholism
• Those with the ALDHY2 gene are much less likely to become alcoholics
due to unpleasant effects – considered the “protective” allele.

27. Multifactorial Disorders
• Schizophrenia
• Risk of Schizophrenia if one parent is affected is 8-10%
• Monozygotic twin studies have a concordance rate of 47%
• Bipolar Disorder
• Risk of Bipolar disorder if one parent is affected is 5-10%
• Monozygotic twins have a concordance rate of 79%
• Some loci have been identified due to pharmaceutical research
• Examples include monoamine oxidase A (MAOA), the serotonin
transporter (5HTT) and catechol-O-methytransferase (COMT)

28. Genetic Testing
Carrier Screening
• Identifies heterozygous
carriers for recessive
diseases.
• People use to help make
reproductive decisions
• Cystic fibrosis, sickle-cell
disease, Tay-Sachs disease
• Carrier Screening has
reduced the prevalence of
some of these diseases
over the past two decades.
Prenatal Diagnosis
• Amniocentesis at 16 weeks
• Chorionic villus sampling
(CVS) at 10-12 weeks
• Pre-implantation genetic
diagnosis (PGD) is carried
out on early embryos prior
to implantation
• Analysis of Fetal DNA in
maternal circulation
available as early as 6
weeks.
• Newborn Screening: PKU

29. Autosomal Aneuploidy
• Down syndrome
• Is the best-known example of aneuploidy.
• Trisomy 21
• Occurs 1 in 800 live births.
• Manifestations: Mental challenges; low nasal bridge;
epicanthal folds; protruding tongue; flat, low-set ears;
and poor muscle tone.
• Risk increases with maternal age.
• Has an increased risk of congenital heart disease,
respiratory infections, and leukemia.

30. Down Syndrome

31. Sex Chromosome Aneuploidy
• Turner syndrome
• Females have only one X chromosome
• Denoted as karyotype 45,X.
• Characteristics include:
• Absence of ovaries (sterile)
• Short stature
• Webbing of the neck
• Widely spaced nipples
• High number of aborted fetuses
• X chromosome that is usually inherited from the
mother
• Occurs 1 in 2500 female births.
• Teenagers receive estrogen.

32. Turner Syndrome

33. Sex Chromosome Aneuploidy
• Klinefelter syndrome
• Individuals with at least one Y and two X chromosomes.
• Characteristics include:
• Male appearance
• Femalelike breasts (gynecomastia)
• Small testes
• Sparse body hair
• 1 in 1000 male births
• Some individuals can be XXXY and XXXXY; will have male
appearance; abnormalities will increase with each X; can
also have an extra Y chromosome.
• Disorder increases with the mother’s age.

34. Klinefelter Syndrome

35. Need to know!!!
• How to describe the genetic abnormalities and resulting
clinical abnormalities associated with the following diseases:
Down syndrome, Turner syndrome, Klinefelter syndrome, cri
du chat syndrome, Huntington disease, cystic fibrosis,
neurofibromatosis, hemophilia, and Duchenne muscular
dystrophy
• The difference between a genotype and phenotype
• How to describe the following elements of inheritance:
autosomal, sex-linked, carrier, dominant, and recessive.
• Know the cause and possible outcomes for the following
mutations: base-pair substitution, frameshift substitution,
spontaneous mutation, and mutational hotspots.

36. Need to know!!!
• How to Identify and describe the familial tendencies and
contributing environmental factors in the following diseases:
coronary artery disease (CAD), hypercholesterolemia,
hypertension, colorectal cancer, diabetes, breast cancer, and
obesity.
• How to Identify and describe the following complex
multifactorial diseases: Alzheimer disease, alcoholism,
schizophrenia, and bipolar disorder.

37. Questions