Genetic Influence in Disease

Define Gene

a segment of a DNA molecule that is composed of an ordered sequence of nucleotide bases (adenine, guanine, cytosine, thymine)

What are the main functions of genes

coding for synthesis of proteins that influence all aspects of body traits and function

Provide examples of genes

• They include “permanent” proteins such as eye pigment, hair color, and blood type in a developing fetus, as well as more subtle inherited traits like outgoing personality or susceptibility to certain diseases

• There are also “day-to-day” functional proteins such as hormones, antigens, antibodies, enzymes, etc

What occurs when there is a mutation of a gene?

the protein it is responsible for often malfunctions

If the gene that codes for lactase becomes mutated, what might happen?

lactose won’t get broken down and lactose intolerance will occur

How does a chromosome form?

a sequence of nucleotide bases forms a gene; genes make up a DNA molecule, and that DNA molecule forms into a specialized shape

How many chromosomes does a person receive from each parent?

23 chromosomes

How many chromosomes does a person end up with?

23 pairs or 46 total

How many pairs of chromosomes are autosomal?

22 pairs

Autosomal chromosome are NOT sex chromosomes & each pair are closely alike. T/F

True

How many pairs of chromosomes are sex chromosomes?

1

Can a pair of alleles be alike?

They are almost exactly alike except that one can be dominant & one can be recessive (or they can both be dominant or both be recessive).

How do we notate recessive genes in autosomal chromosome pairs?

With a lower-case letter

How do we notate dominant genes in autosomal chromosome pairs?

With an upper-case letter

Define genotypes

The combination of genes. Refers to a specific set of alleles

How do we notate homozygous dominant in autosomal chromosome pairs?

GG (both uppercase)

How do we notate homozygous recessive in autosomal chromosome pairs?

gg (both lowercase)

How do we notate heterozygous in autosomal chromosome pairs?

Gg (one uppercase & one lowercase)

Define phenotype

a person’s observable characteristics (anatomic, physiologic, biochemical, behavioral) as determined by genes and environment (not just a physical characteristic).

Define genetic disorders

a disease caused by abnormalities in an individual’s genetic material

Provide two examples for inherited disorders

sickle cell disease & PKD is caused by an inherited, altered (AKA, “mutated”) gene

Provide an example for spontaneous disorders

free radicals form as a result of aging causes damage to the DNA protein synthesis is altered leading to gene mutations an “oncogene” develops which causes rapid, wild proliferation of cell growth cancer may develop

State the ways to categorize genetic disorders

inherited, spontaneous, mitochondrial DNA, multifactorial, chromosomal, & single-gene disorders

Where is DNA found on mitochondrial DNA disorders

majority of DNA is found in nucleus of cells but small bits of DNA are also found in mitochondria

How common are mitochondrial DNA disorders

Not very common

How do multifactorial genetic disorders occur?

combination of environmental triggers and variations / mutations of genes, plus sometimes inherited tendencies

How does cancer occur?

various cancers such as lung cancer: begins by smoke & toxins irritating bronchial tissue one or more genes in cells of that tissue begin to be deranged—oncogenes created code for wild, uncontrolled growth of cells

What are other multifactorial genetic disorders?

many common diseases such as hypertension (HTN), coronary artery disease (CAD) & diabetes mellitus (DM) are now known to be caused or highly influenced by a mix of environmental and inherited components.

What does teratogen cause & what is is?

It is any influence — eg, drugs, radiation, viruses-- that can cause congenital defects

Define congenital defects

They are abnormalities that are either detectable at birth and/or can be attributed to fetal development “glitches

Provide examples for Teratogenic disorders

fetal alcohol syndrome

How does fetal alcohol syndrome occur

It occurs because toxicity of alcohol causes gene mutations during gestational development

What are thalidomide babies

born with abnormal arms and legs due to mothers taking the drug thalidomide during early pregnancy

Define chromosomal disorders

a type of genetic disorder that results from alterations to the development or structure of a chromosome, which in turn alters the “local” genes (genes in the immediate area)--the genes’ functionality is disrupted and they don’t code proteins correctly, giving rise to the phenotype (S&S) of the disorder

What part of the chromosomes do chromosomal disorders affect?

Either the structure or numbers of chromosomes

Define Down’s syndrome

It is a disorder of abnormal numbers of chromosomes that is sometimes associated with pregnancies of women >35 years old

When does Down’s syndrome occur

It occurs in very early cellular division and chromosomal distribution of a fertilized egg: instead of ending up with the normal number--46 chromosomes-- the fetus ends up with 47

Where does the extra chromosome occur at in Down’s syndrome?

the extra chromosome occurs at site #21 -- the 21st chromosome set has three chromosomes instead of two

What is another name for the type of down with an extra chromosome?

Trisomy 21

What is the phenotype for trisomy 21?

It includes mental retardation and typical physical characteristics such as low-set ears, epicanthic fold to the eyes, short limbs, and a larger-than-normal tongue

What is Philadelphia chromosome?

alterations to STRUCTURE of chromosomes

How are chromosomal aberrations caused?

by alterations in chromosomal structure, such as deletion, duplication, or rearrangement of gene sites (translocation) on the chromosome

Why do single-gene disorders occur?

usually due to an inherited mutated gene

What type of recognizable patterns are single-gene disorders inherited in?

autosomal recessive, autosomal dominant, and sex-linked

Why do autosomal recessive disorders occur?

occurs when a mutated (“diseased”), recessive (“weak”) gene partners up with an allele that is also recessive & diseased; those alleles are notated with two lower-case letters

What will happen to the protein that is coded for in autosomal recessive disorders?

It will malfunction & an abnormality/ disease/ disorder will occur that relates to that “bad” protein

Provide an example for autosomal recessive disorder

sickle cell anemia

How does sickle cell anemia occur?

if during fertilization a person inherits a sickle-cell disease gene from mom – ie, a recessive, mutated Hgb-coding gene – and ALSO inherits a sickle-cell disease gene from dad, this person would have a homozygous genotype of the recessive sickle cell genes: dd MUST HAVE INHERETED FROM MOM AND DAD

How do the abnormal recessive alleles in sickle cell anemia affect the RBCs?

those abnormal recessive alleles will code for abnormally-shaped Hgb (sickle-shaped), which will make the RBCs sickle-shaped. B/C these RBCs do not have the usual round & smooth shape, they’re more easily damaged as they go through the blood stream; ultimately this results in less-than-normal numbers of RBCs—this is the definition of anemia.

What are the S&S of sickle cell anemia

SOB , weakness & fatigue, but also ischemic pain (especially in the joints)

Why does SOB, weakness & fatigue occur in sickle cell anemia?

due to decreased O2 being carried to tissues of the body; this decreased carrying capacity is because of anemia: less numbers of RBCs to carry the Hgb which in turn carries the O2 & deformed Hgb simply cannot carry the usual numbers of O2 molecules

Why does ischemic pain (especially in the joints) occur in sickle cell anemia?

the deformed RBCs “clog” up the capillaries that usually carry O2-rich blood to the tissues & this results in distal tissues that are starved of O2 & “cry out” in pain

How does heterozygous genotype for sickle cell anemia occur?

if during fertilization a person inherits a sickle-cell disease gene from one parent but a normal Hgb-coding gene from the other parent, the person’s genotype for Hgb would be: Dd. We know that because the NORMAL gene is dominant over the sickle-cell recessive gene, the person will NOT have the disease but they may pass on the gene to offspring.

Explain how homozygous normal works in inherited disorders

someone with the genotype DD doesn’t have to worry about either having the disease or passing it on

Why does autosomal dominant disorders occur?

occurs when a person inherits a mutated, diseased gene that is dominant

Provide an example for autosomal dominant disorders

polycystic kidney disease (PKD)

How does polycystic kidney disease (PKD) occur?

if during fertilization a person inherits a kidney tissue gene that has a mutation, that gene will “want” to code for abnormal kidneys. in a dominant disease such as PKD, the mutated gene is the strong one, so even if it is paired with a normal allele, it will override the normal allele’s coding

How does polycystic kidney disease (PKD) affect a person?

this results in the kidney tissue developing cysts, which can reduce various kidney functions and lead to kidney failure as a person goes through life

How does the genotype notation work with PKD?

if we use the letter “P” to designate PKD, the genotype for someone that HAS the disease would look like this: PP or Pp.

What is the genotype notation for homozygous recessive in PKD?

a genotype of pp (homozygous recessive) would NOT have the disease

What are the S&S in polycystic kidney disease (PKD)?

• hematuria (blood in urine), proteinuria & frequent kidney infections

• pain at costovertebral anglmany ales and abdomen

  • kidney stones

What is Recombinant DNA?

a form of genetic engineering

How did recombinant DNA occur?

many alterations in DNA came about as a natural part of evolution, but now we can deliberately alter DNA in the interests of medicine and science

What is the current application for recombinant DNA?

• human growth hormone for children lacking it.

• exogenous (“from outside the body”) insulin for diabetics.

• factor VIII for hemophiliacs.

• drugs like tPA & tenecteplase—given as “clot-buster” in patients having a myocardial infarction (MI, aka heart attack).