TNBGGA: The No Bullshit Guide to Genetic Analysis

User Tools

Site Tools

Trace: • chapter_05
chapter_05

Differences

This shows you the differences between two versions of the page.

Link to this comparison view

Both sides previous revisionPrevious revision
Next revision		Previous revision
chapter_05 [2024/08/20 00:03] – mikechapter_05 [2025/02/19 07:57] (current) – mike
Line 1: Line 1:
-<typo fs:x-large>Chapter 05. Defining genes by position</typo>+<-chapter_04|Chapter 04^table_of_contents|Table of Contents^chapter_06|Chapter 06->
  
-Besides providing experimental evidence for chromosome theory as discussed in [[chapter_03|Chapter 03]], Morgan's research group also demonstrated that genes (usually) have fixed positions on chromosomes. When we think about gene position, the term locus (plural: loci, pronounced "LOW-sigh") is sometimes used as a term to describe a gene in the context of its position rather than its function.+<typo fs:x-large>Chapter 05. Defining %%genes%% by position</typo> 
 + 
 +Besides providing experimental evidence for chromosome theory as discussed in [[chapter_04|Chapter 04]], Morgan's research group also demonstrated that genes (usually) have fixed positions on chromosomes. When we think about gene position, the term locus (plural: loci, pronounced "LOW-sigh") is sometimes used as a term to describe a gene in the context of its position rather than its function.
  
 ===== Recombination between two sex-linked genes ===== ===== Recombination between two sex-linked genes =====
Line 72: Line 74:
 The tiny $Y$ chromosome does not contain either the $cv$ or $w$ genes (in fact, the $Y$ chromosome barely has any genes). Thus, for genes on the $X$ chromosome such as $cv$ and $w$, examining males only makes it effectively a test cross. If $cv$ and $w$ segregated independently from each other (i.e., if they followed Mendel's Second Law) we would expect that the four combinations of progeny classes ($cv^+ \ \ w^+$, $cv^+ \ \ w^-$, $cv^- \ \ w^+$, $cv^- \ \ w^-$) would appear at the same frequency; that is, the four progeny classes would show 1:1:1:1 ratio. However, we find that there are more males that are parental-like ($cv^+ \ \ w^-$, $cv^- \ \ w^+$) than there are non-parental (recombinant)-like ($cv^+ \ \ w^+$, $cv^- \ \ w^-$). Specific numbers are given below in Table {{ref>Tab3}}. Genes on the same chromosome such as $cv$ and $w$ do not assort independently if they are located close to each other; they are biased to assort together most but not all of the time. Such behavior is known as linkage.  The tiny $Y$ chromosome does not contain either the $cv$ or $w$ genes (in fact, the $Y$ chromosome barely has any genes). Thus, for genes on the $X$ chromosome such as $cv$ and $w$, examining males only makes it effectively a test cross. If $cv$ and $w$ segregated independently from each other (i.e., if they followed Mendel's Second Law) we would expect that the four combinations of progeny classes ($cv^+ \ \ w^+$, $cv^+ \ \ w^-$, $cv^- \ \ w^+$, $cv^- \ \ w^-$) would appear at the same frequency; that is, the four progeny classes would show 1:1:1:1 ratio. However, we find that there are more males that are parental-like ($cv^+ \ \ w^-$, $cv^- \ \ w^+$) than there are non-parental (recombinant)-like ($cv^+ \ \ w^+$, $cv^- \ \ w^-$). Specific numbers are given below in Table {{ref>Tab3}}. Genes on the same chromosome such as $cv$ and $w$ do not assort independently if they are located close to each other; they are biased to assort together most but not all of the time. Such behavior is known as linkage. 
  
-We already know that $cv$ and $w$ are both sex-linked; that is, we know they are physically located on the $X$ chromosome. But when we perform the cross shown in Figures {{ref?Fig2}} and {{ref>Fig3}}, we observe non-parental types in the F2 test cross progeny. Based on the phenotypes of the non-parental classes, the alleles appear to have separated and moved from one $X$ chromosome to the other. This implies that there must have been an exchange of chromosomal material (crossing over) in the F1 heterozygous mother when she went through meiosis to form gametes. +We already know that $cv$ and $w$ are both sex-linked; that is, we know they are physically located on the $X$ chromosome. But when we perform the cross shown in Figures {{ref>Fig2}} and {{ref>Fig3}}, we observe non-parental types in the F2 test cross progeny. Based on the phenotypes of the non-parental classes, the alleles appear to have separated and moved from one $X$ chromosome to the other. This implies that there must have been an exchange of chromosomal material (crossing over) in the F1 heterozygous mother when she went through meiosis to form gametes. 
  
 ==== Tying a sex-linked cross back to meiosis ==== ==== Tying a sex-linked cross back to meiosis ====
Line 94: Line 96:
 $$\text{map distance} = 100 \times \frac{\text{crossover gametes}}{\text{total gametes}}$$ $$\text{map distance} = 100 \times \frac{\text{crossover gametes}}{\text{total gametes}}$$
  
-In essence, map distance between two points is the percent recombination between those two points. We typically use the unit of measures m.u. (which stands for map unit) or cM (centiMorgan, named in honor of Thomas Morgan) for map distances. We can map the distance between $cv$ and $w$ by doing the cross shown in Figs. {{ref>Fig2}} and {{ref>Fig3}} and carefully counting the number of offspring and their different phenotypes (Table {{ref>Tab3}}). We look at males only:+In essence, map distance between two points is the percent recombination between those two points. We typically use the unit of measure m.u. (which stands for map unit) or cM (centiMorgan, named in honor of Thomas Hunt Morgan) for map distances. We can map the distance between $cv$ and $w$ by doing the cross shown in Figs. {{ref>Fig2}} and {{ref>Fig3}} and carefully counting the number of offspring and their different phenotypes (Table {{ref>Tab3}}). We look at males only:
  
 <table Tab3> <table Tab3>
Line 123: Line 125:
   - Maps are internally consistent and concise.    - Maps are internally consistent and concise. 
  
-The first genetic map of any kind was constructed in 1911 by Alfred Sturtevant when he was a sophomore undergraduate student in Thomas Morgan’s lab. It showed the relative positions of several genes on the Drosophila $X$ chromosome. +The first genetic map of any kind was constructed in 1911 by [[wp>alfred_sturtevant|Alfred Sturtevant]] when he was a sophomore undergraduate student in Thomas Morgan’s lab. It showed the relative positions of several genes on the Drosophila $X$ chromosome. 
  
 <figure Fig5> <figure Fig5>
 {{ :first-genetic-map-sturtevant-1913-49.png?400 |}} {{ :first-genetic-map-sturtevant-1913-49.png?400 |}}
 <caption>  <caption> 
-\The first genetic map, created by Alfred Sturtevant in Thomas Morgan's research lab. The gene symbols in the figure are non-standard; they represent genes that we know today as: B, $yellow$; C, $white$; O, an allele of $white$; P, $vermillion$; R, $mini$; M, $rudimentary$. The numbers represent map positions, and map distances between genes can be obtained by subtracting the numbers. Source: Sturtevant, A.H. (1913). J. Exp. Zool., 14:43-59. Licensing: free for scholarly use from the [[https://www.esp.org/|Electronic Scholarly Publishing Project]]. Commercial use is prohibited without permission.+The first genetic map, created by Alfred Sturtevant in Thomas Morgan's research lab. The gene symbols in the figure are non-standard; they represent genes that we know today as: B, $yellow$; C, $white$; O, an allele of $white$; P, $vermillion$; R, $mini$; M, $rudimentary$. The numbers represent map positions, and map distances between genes can be obtained by subtracting the numbers. Source: Sturtevant, A.H. (1913). J. Exp. Zool., 14:43-59. Licensing: free for scholarly use from the [[https://www.esp.org/|Electronic Scholarly Publishing Project]]. Source claims copyright and that commercial use is prohibited without permission; publishing date suggests image is now in the public domain. 
 </caption> </caption>
 </figure>  </figure> 
  
-<figure>+<figure Fig6>
 {{ :drosophila_genetic_map.png?400 |}} {{ :drosophila_genetic_map.png?400 |}}
 <caption> <caption>
Line 145: Line 147:
 The actual relationship between genetic distance in cM and physical distance in base pairs (bp) of DNA depends on the recombination rate, which is different for different organisms. For example, in humans the recombination rate is 1.3 cM/Mbp whereas in yeast it is 360 cM/Mbp (1 Mbp = 10<sup>6</sup> bp). Sometimes recombination rates in the male and female of a species are different. In Drosophila there is no recombination in males so the genetic distance between markers on the same chromosome are always zero when examined by meiosis in the male. In humans the recombination rate (and therefore map distances) in females is twice that of males.  The actual relationship between genetic distance in cM and physical distance in base pairs (bp) of DNA depends on the recombination rate, which is different for different organisms. For example, in humans the recombination rate is 1.3 cM/Mbp whereas in yeast it is 360 cM/Mbp (1 Mbp = 10<sup>6</sup> bp). Sometimes recombination rates in the male and female of a species are different. In Drosophila there is no recombination in males so the genetic distance between markers on the same chromosome are always zero when examined by meiosis in the male. In humans the recombination rate (and therefore map distances) in females is twice that of males. 
  
-Another issue that often causes confusion concerns the map distances of genes that are far apart on the same chromosome. The physical length of a genetic interval is proportional to the frequency of crossovers that occur in that interval during meiosis. But in a cross, we are not actually counting crossovers; rather, we are counting the number of recombinant progeny that are produced. The frequency of recombinants provides a good approximation of distance for short intervals but as the interval length increases, double or even triple crossovers are possible, making the relation¬ship between frequency of recombinants and crossovers not linear. This is discussed further in [[Appendix_A|Appendix A]] on tetrad analysis.+Another issue that often causes confusion concerns the map distances of genes that are far apart on the same chromosome. The physical length of a genetic interval is proportional to the frequency of crossovers that occur in that interval during meiosis. But in a cross, we are not actually counting crossovers; rather, we are counting the number of recombinant progeny that are produced. The frequency of recombinants provides a good approximation of distance for short intervals but as the interval length increases, double or even triple crossovers are possible, making the relationship between frequency of recombinants and crossovers not linear. This is discussed further in [[Appendix_A|Appendix A]] on tetrad analysis.
  
 ===== Unlinked genes ===== ===== Unlinked genes =====
chapter_05.1724137392.txt.gz · Last modified: 2024/08/20 00:03 by mike