Genetics Quiz Blueprint

Question 1

Epigenetics & alterations in epigenetics

Question 2

Chromosomal Abnormality examples

Answer 2

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.

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.

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 Down syndrome.
*Chromosomal mutations *Reciprocal: Breaks take place in two different chromosomes, and the material is exchanged.
Fragile sites
*Chromosomes develop breaks and gaps when the cells are cultured in a folate-deficient medium.
*Most have no apparent relationship to disease.
*Fragile X syndrome
*Site is on the long arm of the X chromosome; has an elevated number of repeated DNA sequences.
*Is associated with being mentally challenged; is second in occurrence to Down syndrome.

Question 3

Genetic Cancers (discussion topic)

Answer 3

Common Disease Genetics: Cancers (Breast, Colorectal, Prostate) Breast Cancer Incidence most common at 11.4%
Prevalence approx 4 million women . 1 in 8 women will be diagnosed with breast cancer in their lifetime

Manifestations Breast cancer may present with a painless lump in the breast, changes in breast size or shape, or skin changes on the breast such as dimpling, thickening or redness of the skin, nipple discharge, or pain in the breast area

Prevalence: 1.5 million colorectal cases, 1:21 will be dx’d

The gene that is responsible for familial adenomatous polyposis (FAP) is APC, which accounts for 85% of colon tumors
The gene that is most responsible for Lynch Syndrome is MLH1 or MSH2 (ACS, 2020)

Other genes that could increase the risk of developing colorectal cancer include BRCA1 and/or BRCA2; individuals with BRCA1 have a 50% increased chance of disease (ACS, 2020). - Hereditary Traits: A family history of colorectal cancer or polyps, especially in first-degree relatives, can elevate an individual’s risk of developing the disease by 2-4 times (ACS, 2020)
Manifestations: changes in bowel habits, blood in the stool, abdominal discomfort, unexplained weight loss, and fatigue

Prostate Cancer: Incidence: second most commonly diagnosed cancer in men, with over 1.4 million new cases reported in 2020
Prevalence: over 3.3 million men

It is noted that over 90% of breast cancer cases are not inherited (McCance et al, 2023)

Etiology: The etiology of prostate cancer involves genetic, environmental, and lifestyle factors. - Genetic Links: Certain inherited genetic mutations, such as those in the BRCA1 and BRCA2 genes, have been associated with an increased risk of developing prostate cancer (National Cancer Institute, 2024). - Hereditary Traits: Family history, having a father or brother with prostate cancer or when a first-degree relative was diagnosed with prostate cancer before age 65, increases the person’s risk of cancer (National Cancer Institute, 2024)

Question 4

T1DM genetics (disc topic)

Answer 4

Diabetes Type 1 & Type 2 Defined: Type 1 diabetes is an autoimmune condition where the immune system attacks insulin-producing cells within the pancreas, which leads to little to no insulin production

“Type 1 diabetes mellitus (T1DM) is caused by an autoimmune destruction of the pancreatic B-cells, a process in which autoreactive T cells play a pivotal role, and it is characterized by islet autoantibodies.” (Cerna,M., 2019) The consequence of hyperglycemia or T1DM requires lifelong insulin replacement therapy

A combination of environmental factors and genetics are the cause of Type 1 diabetes mellitus

Type 1 diabetes is a genetic disease with a complex multifactorial heredity, due to the predisposition being determined by the interaction of risk, neutral and protective alleles of about 50 genes in conjunction with environmental factors

The HbA1c lab test refers to the glycated hemoglobin which is a permanent attachment of glucose to hemoglobin molecules and would reflect the patients average plasma glucose exposure over the life of the red blood cells (RBCs), which is approximately 120 days

Question 5

Histones vs Chromatin
related terms/interchangable

Answer 5

Chromatin (DNA + protein) is the complex of DNA, RNA and proteins that make up the structure of chromosomes within a cell nucleus
Euchchromatin: loosely packed region of chromatin and associated with active genes
Heterochromatin: highly condensed region of chromatin and associated with tightly packed, inactive genes

Histones (proteins, +charge) are a group of proteins that are a major component of chromatin.
packaging and organizing DNA
5 protein types: ( H1, H2A, H2B, H3, and H4) affect function and structure of chromatin
abundant in lysine and arginine residues
**role in gene expression regulation, by marking DNA with open or closed signs, influencing the accessibility of genes to be transcribed.

Nucleosome: structural unit formed by segments of DNA (neg charge) wrapped w/ histones

Content from Eric

Question 6

Types of studies applied to genetics

Question 7

Risks of transmitting genetic diseases

Answer 7

Mode of inheritance: a term which is the pattern which genetic disease is inherited through

recurrence risk: When one parent is affected by an autosomal dominant disease (and is a heterozygote) and the other is unaffected, the recurrence risk for each child is one-half
New mutation: if neither parent has it with autosomal dominant, normal allele to a disease-causing allele.

Late onset of mutation: if a parent has it, they have a 50% chance of developing it, and they usually die early.
ie: Huntington’s, Raises ethical questions
inherited trinucleotide repeat mutation

Question 8

Autosomal vs Recessive

Answer 8

Single gene-disease mode of inheritance

Autosomal dominant (involves genes known to occur on the 22 pairs of autosomes)
A Single mutation located on one of the nonsex chromosomes (autosome) that causes disease
Equal impact on sexes affects every generation, usually an affected parent
Transmit to approx half of children (fluctuations)
EX: Huntington’s, Marfan syndrome

Autosomal recessive (involves genes known to occur on the 22 pairs of autosomes)
Two copies of the mutated gene (one from each parent) on an autosome to cause disease
ex: Cystic fibrosis, sickle cell anemia

X linked dominant: a single copy of the mutated gene on X chromosome
F>M affected fathers cannot pass to their sons but will pass it to all daughters
ex: Rett syndrome, Fragile X syndrome

X linked recessive: two copies of the mutated gene are required for a female to express this disease but only one for a male
M>F; female carriers usually don’t show symptoms but may pass to offspring; fathers cannot pass to their sons but may pass to their daughters (fathers only pass X to daughters)

Question 9

Application of a Punnet Square

Question 10

Transcription (1) vs Translation

Answer 10

Occcurs in nucleus of eukaryotic cells
*RNA is synthesized from the DNA template via RNA polymerase.
*binds to the promoter site on DNA.
* RNA seeks out ribosome in cytoplasm (assemby/production line of protein synth.)

*DNA specifies a sequence of mRNA. (attaching to ribosomal RNA through ribosome.
*At the same time, amino acids are carried into ribosomes by tRNA, *Creating polypeptide chains

*Transcription continues until the termination sequence is reached. (tRNA is immature)

*Gene splicing occurs. (Immature RNA modified to remove Introns, then reassembled and sent to cytoplasm)
Introns and exons (carry info for protein synthesis)
*mRNA then moves out of the nucleus and into the cytoplasm.

Main players: STOP codon’s-marking the protein at which process will end.

*There are 20 amino acids and 20 tRNA’s
Assemble proteins
Fold and transport
*Folding: molecular chaperones
Oversee protein behavior to make sure its not unfolded, if it does:
a. Denaturation: unfolding and attaching to another protein (ie: egg whites turning white)
b. Disease: ie Alzh. or heat/chem exposure

Question 11

Transcription vs Translation (2)

Answer 11

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.

Question 12

Basic concepts of chromosomal aberration

Answer 12

Euploid cells (normal # of chrom)
*Haploid and diploid cells are euploid forms.

Polyploid cells: An euploid cell has more than the diploid number.
Triploidy: Is a zygote that has three copies of each
chromosome. (69 chromosomes total)
Tetraploidy: Has four copies of each chromosome (92 total).
**Neither survive, still born, or spont abort

Aneuploidy (lack of normal amount of chromosomes)
*Is a somatic cell that does not contain a multiple of 23 chromosomes.
Trisomy (trisomic): Is a cell that contains three copies of one chromosome. (infants can survive)
Monosomy: Is the presence of only one copy of any chromosome. (often fatal.)

Nondisjunction: Is usually the cause of aneuploidy.
failure of homologous chromosomes or sister chromatids to separate normally during meiosis or mitosis.
1 pair of chromosomes missing OR paired elsewhere

Aneuploidy of sex chromosomes
Usually presents less serious consequences than autosomes.
Y chromosome usually causes no problems since it contains little genetic material.
For the X chromosome, inactivation of extra chromosomes largely diminishes their effect

Question 13

Nondisjunction vs translocation

Answer 13

Nondisjunction: usually the cause of aneuploidy.
Failure of homologous chromosomes or sister chromatids to separate normally during meiosis or mitosis (1 pair of chromosomes missing OR paired elsewhere)
Produces gametes
1. Have 2 copies of a chrome.
2. Have 0 copies of a chrome
Gamete + normal haploid= the resulting zygote is mono- or tri-somic for that chrome.

Translocation: the interchange of genetic material between nonhomologous chromosomes.
2 types: Robersonian and Reciprocal

*** Robertsonian: Long arms of two nonhomologous chromosomes fuse at the centromere, forming a single chromosome; (short arm lost completely in 2nd div)
*is common in Down syndrome. (3-5% of cases)
13, 14, 15, 21, 22 (short arms too small w/ no ess. genetic material)
Presents: normal
*The carriers of Robertsonian translocations are unaffected, however their offspring may have serious monosomies or trisomies.

• Reciprocal: Breaks take place in two different chromosomes, and the material is exchanged.
  (The carrier of a reciprocal translation is usually normal, but their offspring can have duplications and deletion)

Ring Chromosome: when telomeres of each arm have been deleted and broken ends fuse together in a ring.
*Triggers series of breakage, fusions, and bridge-events, which continues breakage down the line.
*Ring is NOT dangerous, but following series of breakage is
*P: diverse symptoms, FTT (mild-sev)
C : iodinized radiation, chem exp to affected chrome.

Question 14

Review page 168

Question 15

Sex chromosome aneuploidies

Answer 15

Nondisjunction caused by the failure of homologous chromosomes to separate normally during meiosis

Usually presents less serious consequences than autosomes.
Y chromosome usually causes no problems since it contains little genetic material.
For the X chromosome, inactivation of extra chromosomes largely diminishes their effect

Ex: Turner syndrome (XO), Klinefelter syndrome (XXY), trisomy X (XXX), XYY, and XXYY.

Question 16

Klinefelter syndrome

Answer 16

Klinefelter syndrome
* Individuals with at least one Y and two X chromosomes. (47XXY Karotype)
C: nondisjunction of X chromosomes in mother (increases w/ maternal age)

Characteristics include:
* male appearance.
* femalelike breasts (gynecomastia).
* small testes. (sterile)
* sparse body hair.
* 1 in 1000 male births.
* Long limbs
* 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
**Can show up in next generation

@Chrom. can be lost or interchanged or duplicated; Altered d/t small amt of genetic material involved

Question 17

Beckwith-Weidemann syndrome

Answer 17

Etiology
Chromosome 11: 2 paternal copies and no maternal copies; Doubles insulin-like growth factor 2 (Leads to large for gestational age and hypoglycemia)

Pathophysiology - mechanisms of disease
Overgrowth condition accompanied by predisposition to cancer

Manifestations
Large for gestational age
Neonatal hypoglycemia
Large tongue
Creases on earlobe
Omphalocele
Abdominal organs outside the body in a sac
Hemihyperplasia
One side of the limbs growing larger than the other

Diagnostics
Clinical exam at birth
Genetic testing

Clinical course and complications
Macrosomia (Assess height, weight, and head circumference)
Hypoglycemia (Assess fasting blood sugar)
Macroglossia and cleft palate - feeding and airway concerns (ENT and plastics to repair)
Abdominal abnormalities and kidney tumor concerns (Abdominal ultrasound and serum AFP levels)
Gross motor skills (PT/OT)
Speech and swallowing difficulty (SLP)
Cardiomyopathy and congenital heart defects (EKG, echocardiography)

Question 18

Fragile X syndrome

Answer 18

**Fragile X Syndrome can occur here
long arm of the X chromosome; has an elevated number of repeated DNA sequences.
O: 1:400 male and 1:8000 female
* Is associated with being mentally challenged;
*is second in occurrence to Down syndrome.
if female inherits, trait may be expressed or passed on
if male, it WILL be expressed

Question 19

Commonality between AD and AR disorders

Answer 19

Autosomal dominant inheritance (p. 156)
Diseases are rare.
Occurs in fewer than 1 of 500 individuals.
The union of a normal parent with an affected heterozygous parent usually produces the affected offspring.
An affected parent can pass either a disease gene or a normal gene to his or her children; each event has a probability of 0.5; on average, half will be heterozygous and will express the disease and half will be normal.

Germline mosaicism
2 or more offspring have autosomal dominant disease when the family has no history of disease
Parent carries the mutation in his or her germline but does not actually express the autosomal dominant disease but transmits it to his or her offspring

Characteristics of autosomal dominant inheritance:
* Condition is expressed equally in males and females (not sex-related), and males and females are equally likely to pass the gene to his or her offspring.
* Approximately one-half of children of an affected heterozygous parent will express the condition (all or none of the children may have the condition).
* No generational skipping occurs

Autosomal dominant inheritance recurrence risk:
The probability that a family member will have a genetic disease
When 1 parent is affected by an autosomal dominant disease and the othe is normal, the occurrence and recurrence risks for each child are one half
Each birth is an independent event

New mutation: when no history of an autosomal dominant condition is present but the child develops the mutation
Parent’s subsequent offspring is not greater than that of the general population
Offspring of the affected child will have recurrence risk of one half

Question 20

Commonality between AD and AR disorders

Answer 20

Penetrance (p. 157)
Is the percentage of individuals with a specific genotype who also express the expected phenotype.; i.e. retinoblastoma: eye tumor in children w/ incomplete penetrance

Incomplete penetrance
* Individual who has the gene for a disease but does not express the disease
* Example: Retinoblastoma (eye tumor in children) (90%)
Age-dependent penetrance
* Does not express a disease until a certain age is reached.
* Example: Huntington disease

*single gene disease with severity change: systic fibrosis (severity changes based on individual)

**transmission patterns of a single gene are autosomal dominant inheritance disorders; if you have one allele encoding protein you will have the disease

Expressivity (p. 157)
Is a variation in a phenotype associated with a particular genotype.
Can be caused by modifier genes, environmental factors, and mutations.
**Example: von Recklinghausen disease
* Is autosomal dominant.
* Expressivity varies from brown spots on the skin to malignant tumors, scoliosis, gliomas, and neuromas.

*different races represent different expressions and penetrance i.e. african american’s & sickle cell
*marfans’s is expressed in numerous abnormalities

Question 21

Commonality between AD and AR disorders

Answer 21

Autosomal Recessive Inheritance (p. 158-159)
Punnet square p. 160
Rare but individuals are carriers
Abnormal allele is recessive and the person must be homozygous to express the disease
Appears in children not in the parents
i.e: cystic fibrosis
Gene forms chloride channels w/ defective transport, which leads to a salt imbalance that results in abnormally thick, dehydrated mucus. The lungs and pancreas are affected; the person does not survive past 40 years of age.

Characteristics:
* Condition is expressed equally in males and females.
* Is observed in siblings but not in parents.
* Approximately one-quarter of offspring will be affected.
* Consanguinity may be present.
* Marriage between related individuals