HNPCC, Mendelian Genetics, and DNA Replication: Key Concepts for Biology

What is cancer?

Uncontrolled cell growth and division, often leading to tumors or polyps.

What is HNPCC?

Hereditary nonpolyposis colorectal cancer (Lynch Syndrome); causes polyps in the colon, average onset age 44.

What causes HNPCC?

Mutations in 4 caretaker genes (MLH1, MSH2, MSH6, PMS2) on chromosomes 2, 3, and 7.

Why is the colon prone to HNPCC-related cancer?

High rate of cell division leads to frequent DNA replication errors; without caretaker genes, damage isn't repaired.

What are the criteria for identifying HNPCC families?

1. At least 3 family members diagnosed with HNPCC. 2. One is a first-degree relative. 3. At least 2 successive generations affected. 4. At least one diagnosed before age 50.

What are screening methods for HNPCC?

Colonoscopy, fecal blood screening, genetic testing, genome sequencing.

How does the gel lab detect HNPCC mutations?

PCR amplifies the genetic sequence; restriction enzyme digests at mutation site; gel electrophoresis shows cut vs. uncut DNA.

What is a pedigree in the context of HNPCC?

A family tree diagram showing inheritance of traits/diseases; used to trace HNPCC.

What is the role of a genetic counselor in HNPCC?

Advise at-risk individuals based on pedigree and family history; recommend screening or testing.

What are the Day 2 steps in the lab procedure?

1. Load 20 μL per well. 2. Run gel at 135V for 20 min. 3. Stain with Carolina Blu.

What are the Day 3 steps in the lab procedure?

1. Place gel on light source. 2. Rinse boxes, dry rack. 3. Answer Part 2 questions.

Who is Gregor Mendel?

Father of modern genetics; studied inheritance in pea plants.

What is a character in genetics?

A heritable feature, e.g., flower color in pea plants.

What is a trait?

A variation of a character, e.g., purple or white flower color.

What are true-breeding plants?

Plants that produce offspring identical to themselves every time.

What is Mendel's principle of segregation?

Alleles separate during gamete formation, so each gamete gets one allele.

What are alleles?

Alternative forms of a gene for a trait.

What is the law of segregation?

The two alleles for a gene separate during gamete formation.

What is a dominant allele?

Always expressed if present, represented by a capital letter.

What is a recessive allele?

Expressed only if homozygous, represented by a lowercase letter.

What is a genotype?

Genetic makeup of an individual, expressed in letters.

What is a phenotype?

Physical appearance or observable trait, determined by genotype.

What does homozygous mean?

Both alleles are the same.

What does heterozygous mean?

Alleles are different.

What is a Punnett square?

Diagram to predict offspring genotypes/phenotypes from parental alleles.

What is a monohybrid cross?

Cross involving one trait.

What is the P generation?

Parental generation in a cross.

What is the F1 generation?

First filial generation; offspring of P generation.

What is the F2 generation?

Second filial generation; offspring of F1.

What is the law of independent assortment?

Alleles of different genes segregate independently during gamete formation.

What is incomplete dominance?

Heterozygous phenotype is intermediate between dominant and recessive.

What is codominance?

Both alleles expressed simultaneously in heterozygote.

What are ABO blood types and alleles?

A (i^A i^A or i^A i^O), B (i^B i^B or i^B i^O), AB (i^A i^B), O (i^O i^O).

What is a dihybrid cross?

Cross involving two traits.

What is the rule of multiplication in genetics probability?

Probability of independent events both occurring = product of individual probabilities.

What is a sex-linked gene?

Gene on sex chromosome, usually X.

What is sex-linked notation for color blindness?

Females: X^B X^B (normal), X^B X^b (carrier), X^b X^b (affected); Males: X^B Y (normal), X^b Y (affected).

What is a pedigree?

Family tree diagram tracing inheritance.

What is pleiotropy?

One gene affects multiple phenotypes.

What is epistasis?

One gene affects the expression of another.

What is polygenic inheritance?

Multiple genes affect one phenotype.

What is a testcross?

Cross unknown genotype with homozygous recessive.

What is a carrier?

Heterozygous for recessive disease; no symptoms but can pass to offspring.

What are examples of recessive inherited disorders?

Deafness, albinism, cystic fibrosis, PKU, sickle-cell, Tay-Sachs.

What are examples of dominant inherited disorders?

Dwarfism, Alzheimer's, Huntington's, high cholesterol.

What is Drosophila melanogaster?

A fruit fly common in genetics; has 4 chromosome pairs, XX/XY sex determination, breeds every 2 weeks.

What is the chromosomal theory of inheritance?

Genes are located at specific loci on chromosomes; one chromosome is inherited from each parent.

What are linked genes?

Genes located on the same chromosome that are inherited together unless crossing over occurs.

What is genetic recombination?

The process that produces offspring with new trait combinations through independent assortment or crossing over.

What are parental types vs. recombinant types?

Parental types have the same phenotypes as the parents; recombinant types have new combinations due to recombination.

What is independent assortment?

The principle that genes on different chromosomes separate independently, producing recombinants.

What is crossing over?

The exchange of genes between homologous chromosomes during prophase I of meiosis, creating recombinant chromosomes.

What is a genetic map?

An ordered list of gene locations (loci) on a chromosome.

What is a linkage map?

A genetic map based on recombination frequencies, with map units indicating distance between genes.

What do map units represent?

A unit of recombination frequency; 1 map unit equals a 1% chance of recombination.

What does a 50% recombination frequency indicate about two genes?

They are unlinked, meaning they are on different chromosomes or far apart.

What is X inactivation?

In females, one X chromosome is inactivated, forming a Barr body; explains calico cats' mosaic fur.

What is nondisjunction?

The failure of chromosomes to separate during meiosis, leading to aneuploidy.

What is aneuploidy?

An abnormal number of chromosomes, such as trisomy (2n+1) or monosomy (2n-1).

What is polyploidy?

The condition of having more than two complete sets of chromosomes, e.g., triploid (3n).

What is Down syndrome?

A genetic disorder caused by trisomy 21, characterized by facial features, short stature, and mental disabilities.

What is Klinefelter syndrome?

A genetic condition in males with an XXY chromosome pattern, leading to small testes and sterility.

What is XYY syndrome?

A genetic condition in males characterized by being taller than average with normal intelligence.

What is Trisomy X?

A genetic condition in females with an XXX chromosome pattern, typically healthy and normal.

What is Turner syndrome?

A genetic condition in females with an XO chromosome pattern, leading to sterility and lack of secondary sex characteristics.

What are three fetal screening methods?

Ultrasound, CVS (chorionic villus sampling), and amniocentesis.

What is deletion in chromosome alteration?

A chromosomal fragment that is lost.

What is duplication in chromosome alteration?

A chromosomal fragment that is repeated.

What is inversion in chromosome alteration?

A chromosomal fragment that is reversed.

What is translocation in chromosome alteration?

The switching of fragments between chromosomes.

What is Cri du chat syndrome?

A genetic disorder caused by a deletion on chromosome 5, leading to mental disability and early death.

What is chronic myelogenous leukemia (CML)?

A type of cancer characterized by a translocation between chromosomes 22 and 9.

What is genomic imprinting?

The process where a zygote expresses only one allele based on parental origin.

How are organelle genes inherited?

Mitochondrial DNA is inherited only from the mother.

What is DNA?

Deoxyribonucleic acid; it encodes hereditary information and directs development.

What was Thomas Hunt Morgan's contribution to DNA discovery?

He studied fruit flies in the early 1900s and demonstrated that genes are located on chromosomes.

What was Frederick Griffith's experiment?

In 1928, he showed that harmless bacteria could become pathogenic through transformation.

What did Avery, McCarty, and MacLeod discover?

In 1944, they found that DNA from pathogenic bacteria causes transformation, not protein or RNA.

What was the Hershey-Chase experiment?

In 1952, it confirmed that DNA is the genetic material, as phage DNA enters bacteria, not protein.

What are Erwin Chargaff's rules?

In DNA, the amount of adenine equals thymine, and guanine equals cytosine.

What was Rosalind Franklin's contribution?

In the 1950s, she produced an X-ray crystallography image of DNA showing its helical structure.

What was Watson and Crick's model of DNA?

They proposed the double helix structure of DNA using Franklin's data.

What is the structure of a nucleotide?

It consists of a nitrogenous base, a pentose sugar (deoxyribose), and a phosphate group.

What is the DNA backbone made of?

Sugar-phosphate; the bases attach like rungs of a ladder.

What is the orientation of DNA strands?

DNA strands are antiparallel, running 5' to 3' and 3' to 5'.

What are the nitrogenous bases in DNA?

Adenine (A), Thymine (T), Guanine (G), Cytosine (C).

What are the base pairing rules in DNA?

A pairs with T, and C pairs with G.

What are purines?

Adenine (A) and Guanine (G); they have two organic rings.

What are pyrimidines?

Cytosine (C) and Thymine (T); they have one organic ring.

When does DNA replicate?

During the S phase of interphase, before mitosis or meiosis.

What is semiconservative replication?

The process where new DNA consists of one old strand and one new strand.

What are origins of replication?

Sites where DNA replication begins, forming replication bubbles.

What is a replication fork?

The Y-shaped end of a replication bubble where DNA strands separate.

What is the role of DNA polymerase?

An enzyme that adds complementary nucleotides to the template strand in the 5' to 3' direction.

What is the leading strand?

The DNA strand synthesized continuously toward the replication fork.

What is the lagging strand?

The DNA strand synthesized discontinuously away from the fork, forming Okazaki fragments.

What are Okazaki fragments?

Short segments of DNA on the lagging strand that are joined by DNA ligase.

What is a primer in DNA replication?

A short RNA segment that starts a new DNA strand, synthesized by primase.

What is primase?

An enzyme that synthesizes RNA primers for DNA polymerase.