🚀 go-pugleaf

P J Kennedy (paulk@socs.uts.EDU.AU) wrote:

: Hi all,

: I am a computer scientist trying to understand genetics. With this
: in mind, I have the following questions.

: I understand the term locus to mean the position of a gene on a chromosome.
: For example, if a gene spans the 100th to the 175th base pairs of the
: chromosome then its locus is 100.

: I understand the term allele to mean genes which have different effects
: on a single characteristic that are at the same loci on homologous 
: chromosomes.

I think you will find things less confusing if you avoid the word
"gene" in defining allele -- gene has too many overlapping meanings.

To use a computer analogy:
	Think of a chromosome as a large segment of memory
	Think of a locus as a contiguous range of addresses
	Once you have defined a locus, then each possible
         set of values filling the locus defines an allele.
         In real practice, we can only distinguish alleles if
         we have an assay for them -- some functional characteristic
         classically, but with molecular techniques it is possible
         (though not necessarily useful) to distinguish any two alleles.

: Is the actual locus of a gene on the genetic strip important ?
: From what I understand I don't think it is because a gene will either always
: be expressed (ie. it's constitutive) or it will be turned on or off by other
: genes and this is controlled by what the gene or its promoter looks
: like not its actual position on the strip.

For most genes, the position of the locus on the chromosome is not important
when determining the phenotype generated by a given genotype (set of alleles).

: So if the position isn't important why should alleles be in the same
: position on different chromosomes ? 


: Why should they even be the same length ?
: (Indeed, are they the same length ?) 

This is actually a significant question -- not all alleles of a locus are
necessarily the same length.  Two common classes of null (non-functional)
alleles are those due to the insertion or deletion of genetic material.
However, for most analyses the precise length of the locus isn't important.
I think it is important to remember that locus and allele are abstract
concepts that don't always map perfectly onto biological reality.
For example, a deletion may completely remove a given locus.  For
some types of analysis, we treat this as a null allele at that locus,
whereas for others it is important to treat this as the locus disappearing.
To give another example, an additional means to generate a null allele
is if the locus is the breakpoint of a genetic rearrangement.
If we held strictly to my address analogy, the address range (locus) has
now been subdivided into two non-contiguous segments.  Has one locus
become two?  Well, for most analyses, no.  We just have a null allele.

: Is crossover the mechanism that forces
: genes with similar effects to reside at the same locus ? ie. does crossover
: force alleles ?

Replace "genes" with "alleles".  In one sense, by definition the two
alleles must reside at the same locus (otherwise they aren't alleles).
What you are probably more interested in is the question as to why
genes are organized into consistent chromosomes, 
and its not so much crossing-over
(though crossing-over probably wouldn't occur if they weren't) as
simply the inherent result of how chromosomes are made -- by duplicating
other chromosomes.  

: If, by inversion, an allele of a gene is moved from one locus to another
: position, is it still an allele ? If it is, then the whole definition of
: alleles seems, to me, to be inconsistent.

Again, the inversion moves the locus physically, but in the abstract
sense you still have the same locus (it has the same responsibility).
You might think of genetic loci as defining "genetic space", and 
physical locations (chromosomes) defining "chromosome space".  Alleles
are defined and loci delineated at a time when 
genetic space and chromosome space are interchangable.
Deletions, insertions, rearrangements, duplications, etc break
the interchangability of the two spaces, but the definitions of the
alleles and loci remain fixed.

: Is the garbage information that now fills its old locus an allele ? If it
: isn't (as I would expect) then does that mean that at a particular locus one
: finds either alleles of a gene, garbage or other genes ? 

: Is it right to say that base pairs in the promoter region of a gene can
: serve as some kind of signature for that gene ? For example, if an enzyme
: wants to repress a gene for short hair and the promoter region for the
: short hair gene always contains the sequence AAATTGGGTACG then can the
: enzyme only look for this sequence rather than a much longer one that is
: the actual gene itself ?

Yes.  Transcription factors recognize short sequences, not entire genes.


: Must each of the alleles of a particular gene have the same information
: in the promoter sequence ? By that I mean, do all alleles of a gene have to
: be turned on in the same way and have the same signature ?

No.  Many alleles are defined by alterations in the promoter regions.
These can either eliminate expression (another way to make a null
allele), cause reduced expression, or 
cause inappropriate ("ectopic") expression.



Keith Robison
Harvard University
Department of Cellular and Developmental Biology
Department of Genetics / HHMI

robison@mito.harvard.edu 

What does allele mean ?

While I am not an expert on DNA structure I think you have entirely 
the wrong ideas about alleles and loci (plural of locus).  A locus (as 
I understand it) is a stretch of DNA that codes for example for a 
protein that is one enzyme (I think it may also be used for non-
coding regions e.g. microsatellite loci but that will just confuse 
you) - at one locus there may be different variants of the same 
locus that are called alleles.  In diploid organisms (like us humans) 
we have two copies of our DNA - so we can have at most 2 alleles 
of the same locus.  I have not heard of naming each locus by its 
position e.g. start from base 100 call it locus 100 - for exactly the 
reasons you point out this seems totally impractical as the exact 
position of a gene (or locus) varies even between individuals in the 
same population.  Alleles are variants of the same locus - they may 
have a couple of base pairs changed or maybe and extra base pair 
added (or removed) - but if they are coding for a protein like an 
enzyme then if they are too different (especially in critical places) 
they won't be able to do the "job" (and usually will be selected 
against) - one example of a critical place I assume would be the 
promoter region which turns a gene on.  

To attempt a computer analogy (which is difficult due to my limited 
knowledge) a locus is like a subroutine that does one particular task 
- alleles are different versions of a subroutine written by different 
people (actually more like badly copied versions) while these may be 
slightly different they need to do they same task and link to all the 
other parts of the program in the same way.  Of course a program that 
was anyting like DNA would be considered very poor - heaps of 
irrelevant code that does nothing - two copies of every subroutine!

In article <3bjm7l$ptt@woodstock.socs.uts.EDU.AU> paulk@socs.uts.EDU.AU (P J Kennedy) writes:
>From: paulk@socs.uts.EDU.AU (P J Kennedy)
>Subject: What does allele mean ?
>Date: 1 Dec 1994 05:16:37 GMT


>Hi all,

>I am a computer scientist trying to understand genetics. With this
>in mind, I have the following questions.

>I understand the term locus to mean the position of a gene on a chromosome.
>For example, if a gene spans the 100th to the 175th base pairs of the
>chromosome then its locus is 100.

Well, yes. A locus is the position of a gene. It's localization is NOT, 
however as rigidly set as that - how could it be, when not even all alleles of 
a particular locus are necessarily all the same lenght. 

Think it like this: A chromosome is a desk of drawers, where each drawer is a 
locus (say, called "socks") and an allele is the exact pair of socks you find 
inside. 

>I understand the term allele to mean genes which have different effects
>on a single characteristic that are at the same loci on homologous 
>chromosomes.

See above.

>Is the actual locus of a gene on the genetic strip important ?
>From what I understand I don't think it is because a gene will either always
>be expressed (ie. it's constitutive) or it will be turned on or off by other
>genes and this is controlled by what the gene or its promoter looks
>like not its actual position on the strip.

On the contrary! It's very important! The level of expression depends on the 
situation of the gene in chromosome. The expression pattern depends on 
surrounding genes etc. 

Biological systems are not on/off systems. It is not enough to know whether a 
gene is expressed or not. You need to know when, and to what extent it is 
expressed.

>So if the position isn't important why should alleles be in the same
>position on different chromosomes ?

See above. If your socks are in your "ties" drawer, you gonna look funny when 
you dress up ;-) (Remember, you dress up by the labels on the drawers, not by 
the appearance of the contents.)

>If, by inversion, an allele of a gene is moved from one locus to another
>position, is it still an allele ? If it is, then the whole definition of
>alleles seems, to me, to be inconsistent.

No, the definition of an allele is "the different variations of a gene locus".

>Is the garbage information that now fills its old locus an allele ? If it
>isn't (as I would expect) then does that mean that at a particular locus one
>finds either alleles of a gene, garbage or other genes ? 

Well, yes. It would be an allele. Naturally, If it's total garbage and the 
gene is important, we won't have an individual. A mutant is, by definition, an 
individual with garbage in (one of) it's loci.

>Is it right to say that base pairs in the promoter region of a gene can

Not as simple as that. Most of the finesses are not yet known.

>Must each of the alleles of a particular gene have the same information
>in the promoter sequence ? By that I mean, do all alleles of a gene have to
>be turned on in the same way and have the same signature ?

They don't have to and, indeed, they don't always have. They have very SIMILAR 
sequences, sure - but that is to be expected when one thinks about 
evolutionary processes.

>Thanks in advance for anyone who can help me.

Don't mention it. 

What I can't understand, mind you, is why you come to the net with these 
questions. They can't be answered very well in such a short space. Why don't 
you instead find a good introductory text to genetics? You can read, right?
Try "The Science of Genetics" by Burns, for example. It should be 
comprehensible even with limited background in biology (high-school level 
should be enough).

>Regards,

>Paul Kennedy

>School of Computing Science,
>University of Technology, Sydney.
>--
>------------------------------------------------------------------------------
>Paul Kennedy - paulk@socs.uts.edu.au
>School of Computing Sciences, University of Technology, Sydney.
>PO Box 123 Broadway NSW 2007 Australia.


--
--------------------------------------------------------------------
Ari-Matti Saren at the Institute of Biotechnology, Helsinki, Finland
E-mail (on Internet): saren@operoni.helsinki.fi, Tel +358 0 434 6094
S-mail (home): Ohjaajantie 18 A 2, 00400 Helsinki, Finland
----------------Shikisoku - Zeku, Kusoki - Zeshiki------------------

In article <3bk4l1INNk1q@newsman.csu.murdoch.edu.au> Clare Constantine <constant@csuvax1.murdoch.edu.au> writes:
>From: Clare Constantine <constant@csuvax1.murdoch.edu.au>
>Subject: Re: What does allele mean ?
>Date: 1 Dec 1994 09:22:41 GMT


<SNIP>
>In diploid organisms (like us humans) 
>we have two copies of our DNA - so we can have at most 2 alleles 
>of the same locus.  

Count again. We have two cromosomes each (one from father, one from mother). 
Each chromosome has (during part of the cell cycle) two chromatids. That makes 
4 alleles. From practical point of view we do have two alleles (one in each 
chromosome), but with point mutation and couple of billion truckloads of (bad) 
luck, we may talk about 4 different alleles. 

Yes, I'm nitpicking - no hard feelings, eh? :-)

Ari-Matti 


--
--------------------------------------------------------------------
Ari-Matti Saren at the Institute of Biotechnology, Helsinki, Finland
E-mail (on Internet): saren@operoni.helsinki.fi, Tel +358 0 434 6094
S-mail (home): Ohjaajantie 18 A 2, 00400 Helsinki, Finland
----------------Shikisoku - Zeku, Kusoki - Zeshiki------------------

In <3bjm7l$ptt@woodstock.socs.uts.EDU.AU> paulk@socs.uts.EDU.AU (P J Kennedy) writes:


>Hi all,

>I am a computer scientist trying to understand genetics. With this
>in mind, I have the following questions.

>I understand the term locus to mean the position of a gene on a chromosome.
>For example, if a gene spans the 100th to the 175th base pairs of the
>chromosome then its locus is 100.

>I understand the term allele to mean genes which have different effects
>on a single characteristic that are at the same loci on homologous 
>chromosomes.

>Is the actual locus of a gene on the genetic strip important ?
>From what I understand I don't think it is because a gene will either always
>be expressed (ie. it's constitutive) or it will be turned on or off by other
>genes and this is controlled by what the gene or its promoter looks
>like not its actual position on the strip.

>So if the position isn't important why should alleles be in the same
>position on different chromosomes ? Why should they even be the same length ?
>(Indeed, are they the same length ?) Is crossover the mechanism that forces
>genes with similar effects to reside at the same locus ? ie. does crossover
>force alleles ?
Because you inherit them from your parents on that position on the
chromosome.   They are usually the same length as only insertions or
deletions will increase the length of dna associated with that allele
point mutations don't effect the length of the allele but do affect the
structure and function of the finished product i.e. the protein. 
>If, by inversion, an allele of a gene is moved from one locus to another
>position, is it still an allele ? If it is, then the whole definition of
>alleles seems, to me, to be inconsistent.
>Is the garbage information that now fills its old locus an allele ? If it
>isn't (as I would expect) then does that mean that at a particular locus one
>finds either alleles of a gene, garbage or other genes ? 

>Is it right to say that base pairs in the promoter region of a gene can
>serve as some kind of signature for that gene ? For example, if an enzyme
>wants to repress a gene for short hair and the promoter region for the
>short hair gene always contains the sequence AAATTGGGTACG then can the
>enzyme only look for this sequence rather than a much longer one that is
>the actual gene itself ?
Correct repressers which act on promoters are common e.g. lactose
operon in E.coli. 

>Must each of the alleles of a particular gene have the same information
>in the promoter sequence ? By that I mean, do all alleles of a gene have to
>be turned on in the same way and have the same signature ?

Any change in a promoter will affect the amount of expression of the
gene. Promoters would be expected to be very similar in alleles although
slight variation could occur.
>Thanks in advance for anyone who can help me.


>Regards,

>Paul Kennedy

>School of Computing Science,
>University of Technology, Sydney.
>--
>------------------------------------------------------------------------------
>Paul Kennedy - paulk@socs.uts.edu.au
>School of Computing Sciences, University of Technology, Sydney.
>PO Box 123 Broadway NSW 2007 Australia.

Re: What does allele mean ?
>>Of course a program that 
>>was anyting like DNA would be considered very poor - heaps of 
In article <3bl41n$1he@rebecca.albany.edu> , tivol@tethys.ph.albany.edu
writes:
>	Shannon showed many years ago that putting the maximum information
>through a channel requires redundancy--that is, you increase the
transfer rate
>until some errors occur and use the redundancy to correct them.  Thus
DNA is
>a very good program indeed.  Furthermore, just because most of the DNA
does

I meant if you handed it in as a computer assignment - obviously DNA is
better 
at its function than anything we can yet (or ever?) construct - I think
there are 
lots of fields trying to copy many of its features e.g. designing things 
using "mutation" and selection to find local optimal solutions;
complexity 
theory (put lots of small things together and hope eventually higher
order 
patterns emerge) - don't get me wrong  I think DNA is fascinating!

Alleles are any data in genome mapping experiments which
appear to be distributed within a population according to
Mendelian theory.

    --bks

-- 
Bradley K. Sherman   bks@s27w007.pswfs.gov   510-559-6437, FAX -6440
Institute of Forest Genetics, P.O. Box 245, Berkeley, CA 94701,  USA
<a href="http://s27w007.pswfs.gov/index.html"> Dendrome Project </a>

I think you are getting to technical in a field that is more abstract. 
The position of genetic loci are not measured in base pairs, the are
positioned on a genetic map of each chromosome.  Thus, each gene is
positioned only with respect to other genes.  The distances between genes
are expressed in centi-Morgans (after the great geneticist Thomas Morgan)
and these distances are not actual physical lengths, rather they represent
recombination frequencies between genes.

The position of genes are not necessarily important for their function. 
There is no obvious reason why genes are where they are.   Alleles are on
the same genetic locus by definition.  An allele is really the same gene! 
It is a slight variation of a gene product.  For example, at a single hair
color locus the genes for blonde or brown hair are allelic.  You have one
or the other, but not both.  The actual proteins that these genes encode
are probably slight variations of each other.  Crossing over has nothing
to do with alleles.  Just think of it this way.  If genes did not have
alleles, we would all be identical, as in twins.  Do you understand? 
Humans have all the same genes at the same loci, that is what makes us
human.  However, we have many different combinations of alleles at most
loci, thus we are all a bit different.  Alleles generally are regulated
the same way, by the same promoter sequences.  The differences between two
alleles are really quite small and may only represent a single base-pair
change that may change one amino acid.

Good luck with your studies.

Greg Dressler
Howard Hughes Med. Inst.
Univ. of Michigan, Ann Arbor

Greg Dressler (greg.dressler) wrote:
: The position of genes are not necessarily important for their function. 
: There is no obvious reason why genes are where they are.   Alleles are on
: the same genetic locus by definition.  An allele is really the same gene! 
: It is a slight variation of a gene product.  For example, at a single hair
: color locus the genes for blonde or brown hair are allelic.  You have one
: or the other, but not both.  The actual proteins that these genes encode
: are probably slight variations of each other.  Crossing over has nothing
: to do with alleles.  Just think of it this way.  If genes did not have
: alleles, we would all be identical, as in twins.  Do you understand? 
: Humans have all the same genes at the same loci, that is what makes us
: human.  However, we have many different combinations of alleles at most
: loci, thus we are all a bit different.  Alleles generally are regulated
: the same way, by the same promoter sequences.  The differences between two
: alleles are really quite small and may only represent a single base-pair
: change that may change one amino acid.

I'd like to point out one level of complexity you have left out. While it 
is true that many genes can be shuffled to different positions in the 
genome without any great change in expression, there are a decent number 
of genes that have dramatic change of expression when they are in the 
wrong genetic "neighborhood". It is called "position effects". There is 
something called the locus control region (LCR) which is apart from 
and upstream of the globin locus but is necessary for proper globin 
expression. There may be "reasons" for genes to be located at specific 
physical locations on the chromosome. The basis of this is studies of 
matrix attachment regions (MARs) which have to do with the anchoring of 
chromatin in the nucleus and the higher order packing of DNA. Genes that 
need to be regulated coordinately are sometimes localized together within 
a stretch of DNA that is bounded by MARs. Anyhow, my main point is that 
the position of a gene CAN but does not necessarily impact on the 
expression of the gene.

Gregory S. Turenchalk

Ari-Matti Sar�n (saren@operoni.helsinki.fi) wrote:

: Count again. We have two cromosomes each (one from father, one from mother). 
: Each chromosome has (during part of the cell cycle) two chromatids. That makes 
: 4 alleles. From practical point of view we do have two alleles (one in each 
: chromosome), but with point mutation and couple of billion truckloads of (bad) 
: luck, we may talk about 4 different alleles. 

: Yes, I'm nitpicking - no hard feelings, eh? :-)

: Ari-Matti 

Well, even if the universe aligned to create the incredibly unlikely 
events that you describe, it would still not change the fact that a 
normal diploid individual is never expressing more than two alleles of a 
gene at a time. When there are four potential alleles in the situation 
you are talking about, actually NONE of those alleles are being expressed 
since the chromatin is in a highly condensed and untranscribable state 
(there are a small number few genes that might escape this effect because 
they are necessary for mitosis itself so these are the only possible 
candidates for your four allele nitpicking) 
When the daughter cells  get around to a stage when genes are being 
expressed again, they are once agin diploid with only two alleles to 
express. A Downs syndrome individual would have three alleles for certain 
genes since they are triploid for chromosome 21 but the question was 
focusing on the status quo not the exceptions.

Gregory S. Turenchalk

To Gregory S. Turenchalk

You are entirely correct in your analysis of position effects and locus
control regions.  However, from a geneticists point of view a gene
encompasses more than just the coding region and would include all
elements necessary for correct expression.   It is clear to me that some
of these cis elements are located far from the actual coding region.  Note
that some genes are more than 1 megabase in size.  

I was only trying to explain in very simple terms that the position on a
genetic map generally does not affect the expression pattern.  From the
original questions asked, I think the student has some fundamental
misunderstandings of genetics that may be addressed in more simple rather
than complex terms.

P J Kennedy (paulk@socs.uts.EDU.AU) wrote: 

: Hi all,

: I am a computer scientist trying to understand genetics. With this
: in mind, I have the following questions.

 I find it interesting that this sort of quesiton is being posted by a
computer scientist.  As genome database are constructed it is important
that we share a common vocbaulary so these databases have some sort of
continuity.  The following are definitions that I submit are fairly accurate
and hopefully useful in a broad context.

Locus
 The locus is the specific location of any given sequence of DNA.  This can be
a sequence of known or unknown function that is inherited according to Mendel's
first and second laws.  All of the molecular maps that exist primarily consist
of loci of unknown function.  This is because they are defined by RFLP, RAPD or
microsatellite techniques.  If a specific probe/enzyme combination gives a 
4kb fragment in parent 1 and a 2kb fragment in parent 2, then locus would consit
of two alleles represented by the 4kb and 2kb fragments.  Now if this probe is used
with another genotype (another mapping parent) and a 3kb fragment is recognized, then
a third allele would be defined.  But any one individual would only have
two of the alleles.

Gene
 A locus of known function.  This function could be defined phenotypically such
as the height locus in pea, or molecularly after the gene has been cloned.
Alleles of the genes would be the alternate phenotyic or molecular forms the
gene takes.  The alleles for plant height in pea are tall and short.  The alternate
alleles for a molecularly defined by changes in the DNA sequence via mutation or
deletion or insertion events.  The beta-globin gene change has undergone a 
single A to T mutation to generate the sickle cell anemia phenotype.  The molecuar 
probe for a gene can also be useful to assign the location of the gene on the 
molecular map.  For example, DdeI digestion and probing with the beta-globin region 
will generate bands of 201bp and 175 bp for the normal individual  and a 
single 376bp band for the individual inflicted with Sickle Cell Anemia.  This 
demonstrates how the molecularinformation can be used to place genes on the 
molecular map.

Phil McClean
mcclean@plains.nodak.edu

: The position of genes are not necessarily important for their function. 
: There is no obvious reason why genes are where they are.   Alleles are on
	H'mmmm... I'm not sure that this is necessarily true...  for 
example, take the lactase operon in _E. coli_.  Isn't it true that there 
is an o^c gene that effects the expression of certain parts of the operon 
based on their location relitave to the o^c gene itself?  The expression 
of genes seems to me to be a very complex thing, and a gene will not 
necessarily have the same effect if placed anywhere on the genome.

: the same genetic locus by definition.  An allele is really the same gene! 
	H'mmm/// does that mean an allele ceases to become an allele if 
it changes position by inversion?

: are probably slight variations of each other.  Crossing over has nothing
: to do with alleles.  Just think of it this way.  If genes did not have

	Wow... this seems to me to be wrong, in at least some sense... 
crossing over effects the combination of alleles in an operon, and thus 
the expression of that trait... also, although I'm not sure about this 
(genetics is not my discipline *^_^*) but can't crossing over occur even 
in the middle of a gene?  if there was only a difference of a single 
point mutation in the alleles, I concede this would only yield a change 
in the allele on each strand, but if there were multiple point mutations, 
deletions or additions, or other multiple-base-pair mutations, wouldn't 
the nature of each allele be drastically changed?

: Greg Dressler
: Howard Hughes Med. Inst.
: Univ. of Michigan, Ann Arbor
	thankyou for addresing my concerns,
  Alex Kennedy
  Univ. of Alberta, Edmonton, Alberta, Canada

Gregory Turenchalk (GD 1999) (gturench@minerva.cis.yale.edu) wrote:
: Ari-Matti Sar�n (saren@operoni.helsinki.fi) wrote:

: : Count again. We have two cromosomes each (one from father, one from mother). 
: : Each chromosome has (during part of the cell cycle) two chromatids. That makes 
: : 4 alleles. From practical point of view we do have two alleles (one in each 
: : chromosome), but with point mutation and couple of billion truckloads of (bad) 
: : luck, we may talk about 4 different alleles. 

: : Yes, I'm nitpicking - no hard feelings, eh? :-)

: : Ari-Matti 

: Well, even if the universe aligned to create the incredibly unlikely 
: events that you describe, it would still not change the fact that a 
: normal diploid individual is never expressing more than two alleles of a 
: gene at a time. 

Okay, let's go for the killer example that shows just how delicate
the locus and allele definitions are in the face of biological reality
(i.e. abstract meets concrete and doesn't fare well).

The immunoglobulin (Ig) and T-cell receptor loci are both responsible for
generating enormous amounts of diversity in the immune system.  Each one
of us expresses thousands and thousands of different Ig and TCR proteins.
In addition, for reasons a little too much to go into here, it is
absolutely imperative that the relevant cells of the immune system 
express _one and only one_ Ig (or TCR, depending on the cell type).
How is this accomplished?  First, only one of the two copies of the
locus in question can be expressed; the other is shut down completely
(allelic exclusion).  Second, the variable portions of the antibody are
determined by an irreversible DNA splicing event.  Third, certain constant
regions are later altered by another irreversible DNA splicing event.
Finally, the antibody genes themselves are subject to a heightened mutation
rate and actually evolve during your lifetime.

So, how many Ig alleles and loci does a person have.  The germ line cells
don't undergo any of these processes, and so you could say we each have
a large, elaborate Ig locus.  But at the somatic level, where alleles really
make the difference, we have thousands of different phenotypes, each of 
which should have an allele -- and indeed there is a different DNA molecule
responsible for each different protein.


: A Downs syndrome individual would have three alleles for certain 
: genes since they are triploid for chromosome 21 


Another situation worth mentioning is tumor suppressor genes.  These
are genes whose normal functioning prevents cancer.  Mutant tumor suppressor
genes can lead to cancer, but only if both copies are knocked out.
If you inherit one nonfunctional allele and one functional one, you
are at a high risk for cancer because somatic mutation might change
the functional allele to a non-functional one, and while the chance
of this happening in any one cell is small, multiply that by oodles
of cells and you have a probability near 1.  But there's no strong
reason to expect the new mutant allele to be the same as the old,
and so the unlucky individual now has 3 alleles in all their body, though
any given cell has only 2.

: but the question was focusing on the status quo not the exceptions.

This is the key take-home message.  Locus and allele are abstract concepts
that work well for most situations most of the time if you generalize
a little bit.  But, they are simply not capable of encapsulating all
the beautiful complexity that exists in natural genetic systems.  So
use them in good health, but don't try too hard to squash them into
tight places.  They're just like all those wonderful simplifications
in physics -- after all, physical objects can't really be 0-dimensional
points, yet this approximation works pretty well for a lot of 
calculations.  

Alexander Kennedy (akennedy@gpu.srv.ualberta.ca) wrote:
: : are probably slight variations of each other.  Crossing over has nothing
: : to do with alleles.  Just think of it this way.  If genes did not have

: 	Wow... this seems to me to be wrong, in at least some sense... 
: crossing over effects the combination of alleles in an operon, and thus 
: the expression of that trait... also, although I'm not sure about this 
: (genetics is not my discipline *^_^*) but can't crossing over occur even 
: in the middle of a gene?  if there was only a difference of a single 
: point mutation in the alleles, I concede this would only yield a change 
: in the allele on each strand, but if there were multiple point mutations, 
: deletions or additions, or other multiple-base-pair mutations, wouldn't 
: the nature of each allele be drastically changed?


You are right -- there are two ways to create new alleles by 
crossing-over between two copies of a locus.  One is the situation
you describe -- if intragenic recombination combines differences
at two different locations within the gene.  The other is if 
the crossing-over is imprecise and one copy is shifted relative
to the other before recombination.  This results in one copy 
growing and the other shrinking.

	ABBBBC
          |||		If pairing occurs here
	 ABBBBC

	ABBBBBC		increased by one B
	 ABBBC		decreased by one B

As shown in the diagram, this is most likely to occur if there is
a repetitive region of the gene, and such regions are not uncommon.

Keith Robison
Harvard University
Department of Cellular and Developmental Biology
Department of Genetics / HHMI

robison@mito.harvard.edu 

Greg Dressler (greg.dressler) wrote:

: You are entirely correct in your analysis of position effects and locus
: control regions.  However, from a geneticists point of view a gene
: encompasses more than just the coding region and would include all
: elements necessary for correct expression.   It is clear to me that some
: of these cis elements are located far from the actual coding region.  Note
: that some genes are more than 1 megabase in size.  

Well, an all encompassing definition for a "gene" is controversial. 
Certain distal regulatory elemants such as enhancers may affect more than 
one gene product, so it is difficult to include them as part of the gene 
since they are doing double duty. A definition of a gene needs to take 
into effect that the gene product doesn't necessarily have to be 
translated to do its job (certain genes like XIST <I think> act as RNAs). 

: I was only trying to explain in very simple terms that the position on a
: genetic map generally does not affect the expression pattern.  From the
: original questions asked, I think the student has some fundamental
: misunderstandings of genetics that may be addressed in more simple rather
: than complex terms.

You are right, the original author probably was only asking for 
explanations in basic terms. I just got caught up in the resultant 
nitpicking since I am in the process of trying to earn a PhD in genetics 
and it is a fun way of making a little use of the knowledge they keep 
stuffing in my head ;)

Gregory S. Turenchalk