patho exam one part two

Question 1

transgenerational epigenetic inheritance

Answer 1

the transmission of non-DNA sequence genetic control information from one generation to the next. Genomic imprinting is an epigenetic process whereby DNA methylation and histone methylation patterns are established in the germline of the parent and in that way are passed down to the child and then maintained during mitotic cell division.

Question 2

Global hypomethylation

Answer 2

Found in many cancers, including breast, cervical, thyroid, lung, prostate, bladder, stomach, esophagus, colon, and liver cancer. Hypomethylation of promoter regions upregulates proto-oncogene activity, allowing cancer cells to grow unregulated and metastasize.
It has been hypothesized that hypomethylation promotes overexpression of proto-oncogenes, contributing to an increased risk of cancer and other genes that increase risk for autoimmune disease (ie lupus).

Question 3

Epigenetic mechanisms

Answer 3

influenced by environmental chemical exposure, drugs, aging, and diet. Many genes are silenced during development (in utero or childhood) by methylation, whereas others are turned on by demethylation. As we age, there is a general hypomethylation pattern across the genome, however, there are some gene-specific CpG island hypermethylation sites.

Question 4

Mitochondrial DNA disorder and its genetic role

Answer 4

All mitochondrial DNA comes from the mother. Sperm has very few or no mitochondria and eggs have the usual cellular complement of mitochondria. There is mitochondrial DNA variability within cells because within any person’s cells there are multiple mitochondria with different DNA.

Question 5

Heteroplasmy

Answer 5

The concept of multiple versions of DNA, and mitochondrial DNA in this case, in the same individual and even within a single cell.

Question 6

Leber hereditary optic neuropathy (LHON)

Answer 6

The best known of the mitochondrial disorders. Individuals with LHON have no phenotype at birth or throughout childhood. At 20 to 30 years of age, they begin t have a loss of vision in one eye, which rapidly progresses to blindness and then loss of vision and blindness in the other eye. Children start to lose vision as early as the toddler years in early onset disease, which is less common. If the mother is a carrier, she will pass on some of this mutated DNA to her children. Males with LHON will not pass it on to their children because sperm contributes little to no mitochondrial DNA.

Question 7

DNA replication and direction

Answer 7

The replication of DNA takes place during the S phase of the cell cycle, and there is no difference in the replication process in somatic cells or gametes. The ability of DMA to replicate depends on the unwinding of the double helix, the presence of raw material to make new strands (free nucleotides), and the activity of enzymes that construct the new strands of DNA.

DNA must be constructed beginning with a 5’ end and adding nucleotides sequentially to the 3’ end.

DNA replication does not occur in a linear fashion but rather occurs simultaneously at multiple points along the length of the DNA molecule.

Question 8

DNA transcription

Answer 8

In order for transcription to occur, there must be a DNA template that gives start, sequence, and stop instructions to the RNA polymerase that manages the process.

Question 9

DNA template

Answer 9

The gene is the DNA template and consists of three parts:

a promoter region
the coding region
the terminator region.

Question 10

promoter region

Answer 10

the promoter region instructs the RNA polymerase where t begin transcription as well as which strand of DNA is to be transcribed. The promoter region is not translated into part of the amino acid chain.

Question 11

coding region

Answer 11

The coding region is the portion of the gene that will give rise to the polypeptide chain and eventual protein.

Question 12

terminator region

Answer 12

the terminator region instructs the RNA polymerase where to stop transcribing, and this region is usually transcribed into the pre-RNA.

Question 13

autosomal recessive disorders

Answer 13

in autosomal recessive disorders, both alleles must be the mutated version (the individuals must be homozygous for the mutation) in order to develop the phenotype. One normal copy of the gene makes enough protein to carry out that protein’s function in the body. Individuals who are heterozygous do not express the phenotype, whereas individuals who are homozygous for the mutation do express it. Disorder with an autosomal recessive inheritance pattern may not present in every generation. They appear to skip a generation.

Question 14

Characteristics of autosomal recessive inheritance include:

Answer 14

affected individuals are usually born to unaffected carriers.
both sexes are equally affected
there are fewer affected individuals in a family pedigree.

Question 15

autosomal recessive disorders inheritance pattern

Answer 15

persons with one copy of the mutated gene are known as carriers because they carry the gene and can pass it on to their offspring having an autosomal recessive disorder requires that both parents carry a copy of the mutated gene.
If one parent is a carrier and the other parent is not affected and is not a carrier, with each pregnancy there is a 50% chance that their offspring will be carriers.
If both parents are carriers but neither has the disorder there is a 25% chance that the offspring will have the disorder, 50% chance their offspring will be carriers, and 25% that the offspring will be a nonaffected noncarrier.
In affected individual mates with a nonaffected, noncarrier person, all of the offspring will be carriers but none will be affected or nonaffected noncarriers. The nonaffected, noncarrier parent only has the non-mutated gene to donate and the affected parent only has the mutated gene to donate, so the offspring has one copy of each parent’s gene.
if an affected individual mates with a carrier, with each pregnancy there is a 50% chance their offspring will be affected and a 50% chance the offspring will be a carrier. There is no chance of the offspring being a nonaffected noncarrier because the affected parent always donates a mutated gene.

Question 16

examples of autosomal recessive inheritance pattern

Answer 16

cystic fibrosis
PKU
sickle cell anemia
Tay-sachs disease.

Question 17

X-Linked Dominant Inheritance

Answer 17

This pattern is seen when a gene on the X chromosome exerts dominance, so only one copy is needed to exhibit the trait or disorder.
The difference between X-Linked and autosomal dominant patter is there are not always two copies of the x chromosome- biological males have one X and one Y chromosome, whereas biological females have two X chromosomes. There are sex-related differences in inheritance risk.

Question 18

X-linked dominant risk of inheritance

Answer 18

A heterozygous mom will have the phenotype of the disorder, and there is a 50% chance she will pass it on to each of her offspring regardless of sex.
If the father has the disorder, there is a 50% chance he will pass it on to his female offspring, but no chance he will pass it on to his male offspring because he donates the Y chromosome.

Question 19

X-linked inheritance pattern include

Answer 19

Rett syndrome
fragile X syndrome
X-linked hypophosphatemia (vitamin D-resistant rickets).

Question 20

mRNA and its role in gene transcription

Answer 20

mRNA is transcribed from a gene within the chromatin and used as the template for protein synthesis.
Transcription factors bind and influence the separation of DNA strands and binding of RNA polymerase near the gene promoter region, with subsequent RNA strand elongation until a termination signal is reached. This produces pre-mRNA.

Pre-mRNA is modified with the removal of unexpressed introns by spliceosomes and reconnecting exons that will influence the shape and folding of the protein product. After further modification, the mature mRNA leaves the nucleus to enter the cytoplasm. Once in the cytoplasm, ribosomes attach to mRNA to begin the process of translation.

Question 21

Karyotyping and its role in testing for abnormalities

Answer 21

Karyotyping is a method of depicting, through a standardized presentation, the set of chromosomes for an individual. It is an older genetic technology, but remains useful in identifying chromosomal structural abnormalities.
The laboratory stimulates cells to enter the cell cycle, then stops the cycle during metaphase. The arrested cells are then exposed to a hypotonic solution, which releases the chromosomes from the cell. Next the Giemsa stain that gives the chromosomes their characteristic banding is applied. The chromosome set is then photographed and arranged in the standard order, enabling the study of any abnormalities. Through karyotyping it is possible to identify errors in both chromosome number and chromosome structure.

Question 22

Mitochondrial DNA

Answer 22

Mitochondrial DNA is located in the mitochondria, cellular. It is a circular form and includes genes coding for some proteins of the Krebs cycle and oxidative phosphorylation and hence adenosine triphosphate (ATP) production. Although some proteins used by the mitochondria for energy production are imported from the cytosol, several are made within the mitochondria.
Variability within mitochondrial DNA leads to variable energy production, and there are known variants that lead to poor energy production and drive energy failure in cells with high needs, such as neurons and the lens cells of the eye.

Question 23

Routine screening in newborns for errors in metabolism and genetic disorders

Answer 23

Newborn screening varies from state to state but common genetic disorders tested at birth include several inborn errors of metabolism (in the categories of organic acid disorders, fatty acid oxidation disorder, and amino acid disorders, including PKU. Endocrine disorders (primary congenital hypothyroidism, congenital adrenal hyperplasia); blood disorders ( sickle cell disease, and B-thalassemia); and other common single gene disorders ( cystic fibrosis, classic galactosemia, severe combined immunodeficiencies, and x-linked adrenoleukodystrophy.

Question 24

Epigenetics mechanisms 2

Answer 24

Epigenetics mechanisms are heritable, but they are also modifiable by environmental and interpersonal factors. There is additional variability in epigenetic changes over the life span and specific to each tissue of an individual.

Question 25

epigenetics changes and programming of DNA

Answer 25

A term that has undergone several changes in meaning and has evolved to mean the study of heritable changes that do not involve alterations in DNA sequence. Major mechanisms of epigenetic modification include histone modification, DNA methylation, and noncoding RNA expression.

Question 26

Histone modification in epigenetic mechanisms

Answer 26

Acetylation and deacetylation of histones have been well described. Histone acetylation appears to make the DNA in that region more accessible to transcription factors and promotes gene expression. Deacetylation has the opposite effect such that hypoacetylation decreases transcription. Additional methyl groups (methylation) to histones can also alter, and specifically decrease transcription.

Question 27

Methylation in epigenetics mechanism

Answer 27

The methylation of DNA is a well-studied epigenetic mechanism. The addition of a methyl group to the DNA sequence occurs primarily at the CpG islands sites in the DNA strand where a cytosine (C) is found immediately adjacent to a guanine (G) in the 3’ direction. CpG islands are common in the promoter region, and methylation at these sites can repress transcription of that gene. DNA methylation stabilizes chromatin; hence hypomethylation increases the possibility of DNA damage and dysfunctional repair.

Question 28

Autosomal dominant

Answer 28

One altered copy of the gene in each cell is sufficient for a person to be affected by an autosomal dominant disorder. In some cases, an affected person inherits the condition from an affected parent. In others, the condition may result from a new variant in the gene and occur in people with no history of the disorder in their family.

Huntington disease, Marfan syndrome

Question 29

Autosomal recessive

Answer 29

In autosomal recessive inheritance, variants occur in both copies of the gene in each cell. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition. Autosomal recessive disorders are typically not seen in every generation of an affected family.

cystic fibrosis, sickle cell disease

Question 30

X-linked dominant

Answer 30

X-linked dominant disorders are caused by variants in genes on the X chromosome. In males (who have only one X chromosome), a variant in the only copy of the gene in each cell causes the disorder. In females (who have two X chromosomes), a variant in one of the two copies of the gene in each cell is sufficient to cause the disorder. Females may experience less severe symptoms of the disorder than males. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).

fragile X syndrome

Question 31

X-linked recessive

Answer 31

X-linked recessive disorders are also caused by variants in genes on the X chromosome. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a variant would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).

hemophilia, Fabry disease

Question 32

X-linked

Answer 32

Because the inheritance pattern of many X-linked disorders is not clearly dominant or recessive, some experts suggest that conditions be considered X-linked rather than X-linked dominant or X-linked recessive. X-linked disorders are caused by variants in genes on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), an alteration in the only copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), one altered copy of the gene usually leads to less severe health problems than those in affected males, or it may cause no signs or symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).

glucose-6-phosphate-dehydrogenase-deficiency, X-linked thrombocytopenia

Question 33

Mitochondrial disorders

Answer 33

Mitochondrial inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Mitochondria, which are structures in each cell that convert molecules into energy, each contain a small amount of DNA. Because only egg cells contribute mitochondria to the developing embryo, only females can pass on mitochondrial variants to their children. Conditions resulting from variants in mitochondrial DNA can appear in every generation of a family and can affect both males and females, but fathers do not pass these disorders to their daughters or sons.

Leber hereditary optic neuropathy (LHON)

Question 34

Difference between autosomal, sex linked and mitochondrial disorders.

Answer 34

The key difference between sex-linked and autosomal is that sex-linked inheritance occurs via the genes located on sex chromosomes (X and Y chromosomes) while autosomal inheritance occurs via the genes located on autosomes.
Mitochondrial DNA comes from the mother. There is mitochondrial variability within the cells, because within any individual’s cell there are multiple mitochondria with different DNA.

Question 35

cell membrane lipid barrier

Answer 35

The boundary between intracellular and extracellular fluids is the cell membrane, often referred to as the plasma membrane. The plasma membrane is a complex phospholipid/cholesterol bilayer with a hydrophilic/polar region of phospholipids and cholesterol facing the extracellular and intracellular fluids, and a central fatty acid and cholesterol ring core that is hydrophobic and restricts the passage of polar/hydrophilic solutes. The molecules of cholesterol are interspersed with phospholipids controlling membrane fluidity. It also acts as an electrical insulator that allows separation of electrical charges so that a potential difference or membrane compartments, and as an interface between extracellular messengers and intracellular changes.

Question 36

Which is the best way to describe most human cells

Answer 36

The cell membrane’s lipid barrier allows small nonpolar substances to move between extracellular and intracellular fluid, such as oxygen and carbon dioxide

Question 37

The process of apoptosis is associated with

Answer 37

In apoptosis, the nucleic acids are reduced to fragments and packaged.

Question 38

modes of transport across cell membranes are:

Answer 38

diffusion
Exocytosis
Endocytosis
Facilitated diffusion
Active transport
secondary active transport
aquaporins
ion channels

Question 39

When a substance moves from an area of higher concentration to an area of lower concentration if there is no intervening barrier

Answer 39

diffusion

Question 40

A substance will move across a membrane from an area of higher concentration to an area of lower concentration if it is small and lipid soluble such as oxygen and carbon dioxide.

Answer 40

Diffusion through a membrane

Question 41

phospholipid bilayer-amphipathic molecules with hydrophilic regions pointing toward aqueous extracellular and intracellular fluids, and fatty acid tails making up the hydrophobic core
cholesterol molecules
integral and peripheral proteins
sugary extracellular coat due to glycoproteins and glycolipids.
specialized proteins attached to lipid rafts

Answer 41

Cell membrane features

Question 42

Two layer membrane contains: a nucleolus, most DNA, enzymes, and nucleotides of replication and transcription, transcription factors, pre-m-RNA

Answer 42

Nucleus

Question 43

Manufactured in the nucleus, migrate to the cytoplasm, synthesize proteins in the process of translation, travel freely, or bond to the endoplasmic reticulum (forming rough endoplasmic reticulum).

Answer 43

Ribosomes

Question 44

A system of membranous compartments dispersed throughout the cell contains enzymes of metabolism, and steroid synthesis, a major role in cell calcium storage.

Answer 44

Smooth endoplasmic reticulum

Question 45

The cell death pathway removes unneeded or unwanted cells without activating danger signals and inflammatory responses.

Answer 45

Apoptosis

Question 46

Rapid loss of ATP production, resulting in diminished membrane potential.
Depressed+ Na+/K+ pump activity
Intracellular calcium overload
Cell swelling
Membrane rupture
Loss of antioxidant function
Accumulation of oxygen-derived free radicals (ROS) reactive oxygen species
Acidosis
Activation of degradative enzymes that contribute to membrane rupture and spread of the damage to adjacent cells

Answer 46

Cell death (necrotic cell death in ischemia)

Question 47

1. Nuclear condensation and clumping of DNA.
2. Enzymatic digestion of DNA into segments of uniform length.
3. Nuclear membrane fragmentation.
4. Cell membrane shrinkage-removal of small pieces of membrane and cytoplasm by blebbing.
5. Blebbing proceeds until the entire cell has been replaced by small fragments termed apoptotic bodies
6. Cellular debris and apoptotic bodies are phagocytosed by tissue macrophages.

Answer 47

Steps in Apoptosis

Question 48

1. Cellular Senescence
2. Telomere attrition
3. Genomic instability
4. Loss of proteostasis
5. Deregulated nutrient sensing
6. Mitochondrial Dysfunction
7. Stem cell exhaustion
8. Epigenetic alterations
9. Altered cellular communication

Answer 48

Nine hallmarks of aging

Question 49

Caused by severe trauma or ischemic injury. Cells swell, rupture, spill signals of tissue danger, initiate inflammation

Answer 49

Necrotic

Question 50

Cells shrink, small blebs containing contents break off, noninflammatory

Answer 50

Apoptotic

Question 51

Some cells digest their own contents, provide nutrients for other cells in the surrounding region, and are noninflammatory.

Answer 51

Autophagic

Question 52

Cells reach a replicative limit and can no longer enter the cell cycle for production of daughter cells. Simultaneously signals are upregulated for the cells to be cleared by phagocytic cells.

Answer 52

Cellular senescence

Question 53

related to cellular senescence in that shortening of telomeres at the end of chromosomes means that DNA can no longer be replicated—this ends cell division

Answer 53

telomere attrition

Question 54

failure of DNA repair processes allows DNA damage to accumulate—signaling for cell destruction

Answer 54

Genomic instability

Question 55

turnover of damaged proteins is initiated by binding of the protein ubiquitin and targeting to proteasomes for degradation. Accumulation of damaged proteins is a signal for death by apoptosis

Answer 55

Loss of proteostasis

Question 56

insulin/insulin-like growth factor 1, and sirtuins, are signaling molecules of nutrient lack or sufficiency. Alterations in these signals may relate to the well-described effect of caloric restriction to extend healthy life span in most animal models.

Answer 56

Deregulated nutrient sensing

Question 57

cell energy production may be decreased during aging, while the ability of the mitochondria to initiate apoptosis may increase this pathway with aging

Answer 57

Mitochondrial dysfunction

Question 58

Can reduce the renewal of cells with rapid turnovers such as blood and mucosal cells

Answer 58

Stem cell exhaustion

Question 59

May alter expression of genes associated with aging process

Answer 59

Epigenetic change

Question 60

changes occurring within intercellular signaling.

Answer 60

Altered cellular communication

Question 61

Entire contents of a cell. It is made up of cytosol(intracellular fluid), organelles, and other structural components of the cell.

Answer 61

cytoplasm

Question 62

1. complex phospholipid/cholesterol bilayer with hydrophilic/polar regions of phospholipids and cholesterol facing the extracellular and intracellular fluids, and a central fatty acid and cholesterol ring core that is hydrophobic and restricts the passage of polar/hydrophilic solutes.
2. The membrane is studded with proteins-both integral proteins that span the membrane and proteins attached to the inner or outer membrane.
3. The membrane is dynamic, moving with motile cells such as white blood cells, conducting exocytosis and endocytosis, and enlarging with cell hypertrophy. Membrane proteins can be internalized and recycled, and new proteins can be inserted from vesicles.
4. Lipid raft- a region of tighter lipid and cholesterol packing that tends to move as a cohesive unit. A protein is linked to the lipid raft by a GPI anchor, allowing the protein to be associated with the plasma membrane without actual insertion through the membrane.

Answer 62

characteristics of a cell membrane

Question 63

Mutates into many cancers, particularly those that involve epithelial tissues, such as colon and breast.

Answer 63

EGFR, in addition, some of the downstream proteins activated by EGFR and other growth-related proteins are also mutated in cancers. The Ras protein was one of the first identified oncoproteins. EFGR activation turns on several signaling pathways that ultimately alter gene expression, transcription, and translation to increase rates of cell division. While this growth-promoting action is needed during embryonic and fetal development, it promotes cancer formation when initiated in an unregulated fashion in adulthood. A close relative of EGFR encoded by the HER2/neu gene is ErbB2- this form of EGFR is commonly mutated in breast cancer and has been targeted by specific drugs used in treating these cancers.

Question 64

Primary active transport pump and drugs that inhibit gastric acid secretion.

Answer 64

The proton pump, or potassium-hydrogen ATPase, is involved in the secretion of hydrochloric acid in the stomach and in renal acid-base regulation.  The proton pump is the target of drugs that inhibit gastric acid secretion.
ranitidine (zantac)
famotidine (pepcid)
nizatidine (axid)
protonix

Question 65

means “lack of flesh” Its a condition of age-associated muscle degeneration that becomes more common in people over the age of 50.

Answer 65

Sarcopenia in aging adults

Question 66

The functional unit of contraction of striated muscle (cardiac, and skeletal)

Answer 66

sarcomere

Question 67

Proteins in skeletal muscle

Answer 67

Actin is a protein made up of repeated subunits joined together to form a thin strand, which is further surrounded in a spiral fashion with regulatory proteins troponin and tropomyosin. Myosin is a protein containing two heavy chains and two pairs of light chains. Myosin’s heavy chain tail region forms thick interwoven strands with other myosin molecules, while the movable head region contains binding sites for actin, ATP, and regulatory light chains. Together these proteins are referred to as myofibrils.

Question 68

proteins in smooth muscle

Answer 68

When intracellular calcium increases in smooth muscle cells, it binds to the protein calmodulin. This activates calmodulin, and the calcium/calmodulin complex can then bind to the enzyme myosin light chain kinase, activating the kinase function. Myosin light chain kinase then phosphorylates the regulator light chain of myosin, causing the head to move closer to the nearby actin filament resulting in cross-bridge formation and cell contraction.