bio 207 lec 10
What is the difference between homologous chromosomes and sister chromatids?
Homologous chromosomes are a pair of chromosomes (one from each parent) that have the same genes at the same locations but may carry different alleles.
Sister chromatids are identical copies of the same chromosome, created during DNA replication, and are held together by a centromere.
👉 Think: homologous = same genes, different origin; sister chromatids = identical copies, same origin.
When do sister chromatids and homologous chromosomes separate during meiosis?
Homologous chromosomes separate during meiosis I, specifically anaphase I.
Sister chromatids separate during meiosis II, specifically anaphase II.
👉 Tip: Homologs split first (anaphase I), sisters split second (anaphase II).
what is the principle of segregation (mendels first law)
The Principle of Segregation states that alleles of a gene separate during the formation of gametes, so each gamete receives only one allele from each gene.
👉 This happens during meiosis when homologous chromosomes separate in anaphase I.
What is Mendel's Second Law?
Mendel's Second Law is the Principle of Independent Assortment. It states that genes located on different chromosomes assort independently during gamete formation, creating new combinations of traits.
👉 Applies when genes are unlinked — on different chromosomes or far apart on the same one.
What does independent assortment allow for in evolution?
New allelic combinations, increasing genetic variation.
What is crossing over?
The exchange of DNA between non-sister chromatids during meiosis.
why did crossing over evolve
Crossing over evolved as a way to increase genetic variation by mixing alleles on the same chromosome, which helps populations adapt and evolve over time.
👉 It’s nature’s way of shuffling the deck — even when genes are linked!
When does crossing over occur?
During late prophase I of meiosis.
What is homologous recombination?
The process where alleles on the same chromosome are mixed via crossing over.
Can homologous recombination only occur between homologous chromosomes?
Yes — homologous recombination typically occurs between homologous chromosomes, specifically between non-sister chromatids during meiosis I.
👉 This exchange happens because homologs carry the same genes, allowing precise alignment for crossover.
What are recombinant gametes?
Gametes that have a different allele combination than the parent due to crossing over.
What is a linkage group?
A set of genes located close together on the same chromosome and often inherited together.
recombinantion frequency
between two genes depends on how far
away from each other they are along the chromosome
What determines if genes are linked?
Their physical proximity on the chromosome.
What is the notation for linked genes in a cross?
A line separates the two homologous chromosomes, e.g.,
a b
------
a b
What is a testcross used for in linkage studies?
To determine if two genes are linked by crossing a heterozygote with a double recessive homozygote
What result indicates unlinked genes in a testcross?
50% (25 M + 25 D) parental and 50% recombinant progeny.
What result indicates completely linked genes?
100% parental genotype progeny.
What result indicates partially linked genes?
A majority of progeny with parental genotypes and some recombinants.
Why does a testcross of completely linked or partially linked genes mostly show parental genotypes?
In a completely linked testcross, no crossing over occurs, so only parental genotype gametes are produced.
In a partially linked testcross, crossing over happens rarely, so most gametes are still parental, and only a small percentage are recombinant.
👉 Linkage keeps genes together — unless crossing over breaks them apart.
What does it mean that testcross results are the same if two genes are on different chromosomes (like in Mendel’s dihybrid experiments)?
It means that genes on different chromosomes behave as unlinked, so they assort independently and produce 50% parental and 50% recombinant genotypes — just like if two genes are very far apart on the same chromosome.
👉 Unlinked = independent assortment = 1:1:1:1 ratio in testcross.
Can a testcross tell if two genes are far apart on the same chromosome or on different chromosomes?
No — a testcross cannot distinguish between genes that are on different chromosomes and genes that are far apart on the same chromosome, because both show 50% recombinant frequency due to independent assortment or frequent crossing over.
👉 50% recombination = either unlinked OR far apart on same chromosome.
What is recombination frequency?
(Number of recombinant offspring / Total offspring) × 100%
What is the maximum recombination frequency?
50%, which occurs if genes are far apart or on different chromosomes.
What does a 16% recombination frequency mean with two types of recombinant gametes?
16% of gametes are recombinant; each recombinant type is 8%.
at what frequency would each parental phenotype happen at a recombinant frequency of 16%
42%
What is a genetic map?
A diagram showing the relative positions of genes on a chromosome based on recombination frequency.
What is the probability (multiplication rule) for predicting cross outcomes with linked genes? Give an example.
The multiplication rule says that the probability of a specific offspring genotype = probability of each parent’s gamete × probability of the other parent’s gamete.
Example (linked genes with 16% recombination frequency):
Cross: T D / t d × t d / t d
From the heterozygous parent:
Parental gametes (T D and t d) = 42% each
Recombinant gametes (T d and t D) = 8% each
Probability of getting Tt Dd = 0.42 × 1.0 = 42%
(because the t d / t d parent only makes t d gametes)
👉 Use gamete frequencies from recombination data, then multiply across parents.
What is 1 map unit (m.u.) or centiMorgan (cM)?
A 1% recombination frequency between two genes.
What did Thomas Hunt Morgan contribute to genetics?
He showed crossing over occurred along chromosomes and developed genetic maps. Used fruit flies to study chromosomes and their role in heredity. Nobel Prize in 1933.
What is the relationship between gene distance and recombination?
The farther apart two genes are, the more likely a crossover will occur between them.
physical distances between genes are proportional to
recombination frequency
How can recombination frequencies help determine gene order?
Recombination frequencies reflect the distances between genes — the smaller the frequency, the closer the genes are. By comparing these frequencies between multiple gene pairs, we can figure out the relative order of genes on a chromosome.
Example:
A to B = 5%
B to C = 10%
A to C = 15%
🧠 That means: A — B — C is the correct gene order.
👉 Lower recombination = closer together. Add the distances to find the map order.
Do recombination frequencies tell us the actual physical location of genes on a chromosome?
No — recombination frequencies give us the relative position of genes, not their exact physical location. They create a genetic map, not a physical map.
👉 Genetic maps show distance in % (centiMorgans), while physical maps use base pairs (like megabases, Mb).
What problem arises with mapping genes far apart?
Recombination frequency maxes out at 50%, making distance estimates inaccurate.
Why do maps underestimate long distances between genes?
Because of double crossovers — when two crossovers happen between the same gene pair, they can cancel each other out, making it look like no recombination occurred.
👉 This leads to fewer observed recombinants, so the calculated distance is shorter than the true distance.
Why can’t you tell when a double crossover has occurred?
Because the alleles switch places twice, ending up in the same order as the original (parental) combination. So when you look at the offspring’s genotype, it appears non-recombinant, even though recombination happened.
👉 It’s like undoing a shuffle — the swap is real, but the outcome looks unchanged.
Does a double crossover cause genetic variation?
It can — but not always.
If the double crossover happens between different genes, it can create a new allele combination, adding variation.
But if it happens between the same two points, and restores the original order, then no new variation is seen in the gamete.
👉 Some double crossovers add variation, others are silent — depends where the swaps happen.
Physical maps
s are actual physical locations measured in actual
bases along the chromosome (units Mb, megabase)
Why does it matter that recombination happened if it goes back to normal — wouldn’t the distance be the same as if no recombination happened?
It matters because genetic distance is supposed to measure how often crossing over occurs, not just the visible result. Even if the final alleles look the same as the parent, the fact that two crossovers occurred means the region between the genes is large enough for that to happen.
So if we ignore these hidden double crossovers, we assume less recombination happened than actually did — which makes the genes appear closer together on the map than they really are.
👉 It’s like measuring traffic by only counting the cars you see — if a few take hidden roads and you miss them, it seems like the road is less busy than it actually is.
What is a two-point testcross?
A testcross between two genes to measure recombination frequency and determine if they are linked.
What does a 50% recombination frequency in a two-point testcross mean?
The genes are either on different chromosomes or very far apart on the same one — they assort independently and are not linked.
How can you identify linkage groups using two-point testcross data?
Genes with recombination frequencies less than 50% are likely in the same linkage group. Those with 50% are in different groups.
In two-point testcross data, how do you determine gene order?
Start with the largest distance (highest recombination %) to place genes farthest apart, then insert the remaining gene between them based on other distances.
Why might distances from two-point testcrosses not add up perfectly?
Because recombination frequencies are less accurate over longer distances, often due to undetected double crossovers.
What is a three-point testcross?
A single testcross involving three genes used to determine gene order and map distances more efficiently than multiple two-point crosses.
why would the distance adding up to 30 be more accurate that the calculate recombination frequency of 28
he calculated recombination frequency (like 28%) underestimates the true number of crossovers — so the genetic distance appears shorter than it really is (maybe it’s actually 30 or more).
👉 The farther apart the genes, the more hidden swaps can happen, making our map “look shorter” than it is.
What does “Note: Double crossover, outer alleles same as non-recombinants, but the middle gene alleles recombine” mean?
In a double crossover involving three genes, two crossovers happen — one on each side of the middle gene.
This causes the outer genes (first and third) to stay in the same order as the non-recombinant (parental) chromosomes, but the middle gene gets flipped between them.
👉 That’s why in double crossover offspring, the outside alleles match the parents, but the middle gene is different — and that’s how we find the gene in the middle!
Why can’t A and C just swap instead of B?
Because A and C are outside the crossover regions.
Crossing over only affects the sections of DNA between the crossover points.
Since the double crossover is happening on either side of gene B, it's the only one in the affected segment.
👉 Only DNA between the two crossover points is exchanged — that’s why the middle gene is the one that changes.
Why is a three-point testcross more efficient?
It provides info about gene order and recombination frequencies for three genes in just one cross, saving time and effort.
Step 1 – What do you do first when using progeny numbers to find gene order?
st (eye color)
ss (bristle type)
e (body color)
Identify the non-recombinant progeny — these are the two most common phenotypes. They show the original parental combinations of alleles.
🧪 Example: Let’s say the two most common (highest numbers) phenotypes are:
st⁺ ss⁺ e⁺
st ss e
These are the non-recombinants.
Step 2 – What do the least common progeny tell us in a three-point cross?
They are the double crossover progeny — produced when two crossovers happen, which is rare.
🧪 Example: Let’s say the two least common phenotypes are:
st⁺ ss e⁺
st ss⁺ e
These are double crossovers.
How do you compare double crossover progeny to non-recombinants to find the middle gene?
Compare each double crossover to the non-recombinants. The gene that is different is the middle gene, because in a double crossover, only the middle gene changes.
🧪 Example:
Non-recombinant: st⁺ ss⁺ e⁺
Double crossover: st⁺ ss e⁺
→ Only ss has changed → so ss is the middle gene
Step 4 – What is the correct gene order if ss is the middle gene?
If ss is in the middle, and the original gene combo was:
st⁺ ss⁺ e⁺
Then the gene order is: st – ss – e
Once gene order is known, how are recombination frequencies used?
Once you know the gene order, you calculate recombination frequencies between each adjacent gene pair (using both single and double crossovers), then use those values to build a genetic map.
🧪 Example: Gene order = st – ss – e
Count how many progeny show recombination between st and ss (single and double)
Count how many show recombination between ss and e (single and double)
Add them to get recombination frequencies
Then convert those into map units (m.u. or cM):
Recomb freq (%) = (recombinants ÷ total) × 100
1% = 1 map unit
👉 This gives you the genetic distances between genes and builds the chromosome map.
What are the steps for determining gene order in a three-point cross?
dentify non-recombinant progeny (most common)
Identify double crossovers (least common)
Compare them
The gene that differs is the middle gene
Why are three-point crosses better at detecting double crossovers than two-point crosses?
Because three-point crosses include a middle gene, so you can see when it flips due to a double crossover — something that’s invisible in two-point crosses, where the result may look like a parental genotype.
👉 Three genes = a built-in way to catch swaps in the middle that two-gene crosses would miss.
Do double crossovers between the same interval happen often in three-point crosses?
No — double crossovers in the same interval (like A–B and A–B again) are very rare. Most double crossovers in three-point crosses involve one crossover between A–B and another between B–C, which is exactly what three-point crosses are designed to detect.
Crossover events are random, but they usually spread out along the chromosome.
Two crossovers in the same small region (like between A–B) are much less likely than one crossover on each side of a gene (A–B and B–C).
There's also something called crossover interference — it makes it less likely that a second crossover will happen too close to the first one.
Why would someone use a two-point cross instead of a three-point cross?
Two-point crosses are useful when studying only two genes, or when doing a quick initial screen to detect linkage. They're simpler, require fewer resources, and are good for building linkage groups before constructing full maps. If gene order is already known, two-point crosses can also help refine distances between specific gene pairs.
What is genetic linkage?
Genetic linkage refers to genes located close together on the same chromosome that tend to be inherited together during meiosis.
What causes genetic recombination between linked genes?
Crossing over during prophase I of meiosis, where homologous chromosomes exchange segments.
What is a genetic marker?
A gene with a visible phenotype (e.g., eye color, seed shape) that can be tracked across generations.
What is gene mapping?
Gene mapping is the process of determining the location, order, and relative distances between genes on a chromosome.
What is a molecular marker?
A DNA sequence variation (like STRs or SNPs) used to study gene inheritance when phenotypes are not visible.
What are microsatellites (STRs)?
Short Tandem Repeats — sequences with 2–6 base pairs repeated in a row, found in non-coding regions.
🧪 Used in: (dna fingerprinting) Forensics, paternity testing, gene mapping
Importantly, different individuals will have
different numbers of repeats at a locus
How are microsatellites analyzed?
Use PCR with primers flanking the repeat.
Run product on a gel — different repeat lengths = different band sizes.
Why are microsatellites treated like alleles?
Different individuals may have different numbers of repeats at a locus, similar to how alleles vary.
If humans are 99.9% genetically identical, how can we still be so different?
Although humans share 99.9% of their DNA, the remaining 0.1% difference adds up to over 3 million base pair differences between any two individuals because the human genome is so large (~3 billion base pairs total).
These differences include:
SNPs (single nucleotide polymorphisms)
Insertions/deletions
Microsatellite repeat variations
These variations explain why we differ in:
Appearance (eye color, height)
health and disease risk
Behavior, personality, etc.
What is a SNP (single nucleotide polymorphism)?
A variation at a single nucleotide position in the DNA sequence between individuals.
What is a haplotype?
A haplotype is a group of linked genetic markers (like SNPs) that are physically close together on a chromosome and tend to be inherited together as a block.
What is linkage disequilibrium?
When certain combinations of alleles or SNPs are inherited together more often than expected by chance.
Normally, if recombination was totally random, nearby alleles/SNPs would mix freely over generations.
But if two markers are close together, they’re less likely to be separated by crossing over.
So those combinations (haplotypes) stick together in populations.
What is the goal of a GWAS (Genome-Wide Association Study)?
To identify chromosomal regions associated with diseases or traits by comparing SNP patterns in affected vs. healthy populations.
Humans have ~20,000–25,000 genes. How do scientists find which genes are associated with a disease?
Instead of looking directly at every gene, scientists use Genome-Wide Association Studies (GWAS) to find regions of the genome that are more common in people with a disease. Then they look at what genes are in those regions.
Why are SNPs near a disease gene helpful in GWAS?
SNPs close to the mutation are inherited with it due to limited recombination — like a fingerprint for the disease region.
What does genetic mapping not tell us that physical mapping does?
Genetic mapping shows relative gene order based on recombination, but not the exact physical location on the chromosome — physical mapping does.
What is deletion mapping?
A method using strains with known chromosomal deletions to determine the physical location of a gene.
How does deletion mapping work?
Chromosomes can be stained and have characteristic
banding patterns. deletion mapping is a method using strains with known chromosomal deletions to determine the physical location of a gene.
How does deletion mapping work?
Cross a mutant strain (homo rec) with several deletion strains (het/ wt) . If a deletion overlaps the gene of interest, mutant phenotype appears in some progeny.
🧠 Shortcut: If crossing with deletion strain causes phenotype, the gene must be in the deleted region.
If the mutant phenotype appears:
→ The wild-type gene was missing in the deletion → gene must be in that deleted region.
If the offspring looks normal (wild-type):
→ The wild-type copy was still present → gene is not in the deleted region.
What organism is deletion mapping most used in?
Drosophila (fruit fly) — it has a well-studied genome and deletion strains covering ~78% of euchromatin.
What is FISH (Fluorescence In Situ Hybridization)?
FISH is a physical mapping technique that uses fluorescently labeled complementary DNA or RNA probes to bind to a specific DNA sequence on a chromosome. It allows scientists to directly visualize the location of a gene under a microscope. nucleotides and fluorescent tag are fused
Q: What does it mean to use deletion strains that "tile" the chromosome to map gene locations?
It means using multiple overlapping deletion strains that each remove a different segment of the chromosome, so together they cover (or “tile”) the entire region. This helps pinpoint the exact location of a gene by seeing which deletions reveal the mutant phenotype.