Error is the stochastic variation associated with a particular observation of the phenotype (and is managed by use of replication and and appropriate experimental design). The phenotype is the result not only of the average effect of the differnt alleles at a given locus across test units and across environments, but is impacted by the interaction between the different alleles and the environments (including genetic backgrounds) in which they are evaluated. Phenotype is not simply the sum of the genotype effect and the environment effect, as indicated in the mathematical formula that you provide.

I am specifically referring to the use of multi-environment experiments (for example field trials) involving panels of progenies from bi-parental population(s) to generate phenotype data for use in mapping genomic regions contributing to the genetic control of the trait(s) of interest, which may themselves interact.

A not-so-recent reference that you may seek guidance from is

Yadav, R.S., F.R. Bidinger, C.T. Hash, Y.P. Yadav, O.P. Yadav, S.K. Bhatnagar, and C.J. Howarth. 2003. Mapping and characterization of QTL x E interactions for traits determining grain and stover yield in pearl millet. Theoretical and Applied Genetics 106:512–520.

Another example is the 2012 paper by Federer and Crossa: Walter T. Federer and José Crossa. 2012.. Screening experimental designs for quantitative trait loci, association mapping, genotype-by-environment Interaction, and other investigations. Front Physiol. 3: 156.

Other recent papers on the statistical models appropriate for multi-environment evaluation of large panels of entries for mapping of, for example, drought tolerance of grain yield, have been published by a Generation Challenge Program-supported team at Wageningen.

Please let me know if you need any further clarification.

Best regards,

Tom

Genotype- phenotype relationship means that a single mutation can be linked to a specific type of symptom. When you are studying a disease that is multifactorial, having this kind of genotype-phenotype relationship is really difficult. I hope it helps you!

The right equation is:

Phenotype = genotype + ambient

The situation is made very complicated by several factors. In addition to the influence of the environment, the mechanisms of regulation of gene expression and the action of other regulatory genes or genes functionally connected may play a role. For this reason some diseases that are genetically determined may show a reduced penetrance or a variable expressivity.

How well can a genotype account for an observed phenotype ? This seemingly simple question is actually a very complex one. some of the reasons are :

1. phenotype is a result of genotype, environmental factors and stochastic factors interacting at various levels. each factors are multi-dimentional in itself.

2. the definition of phenotype is broad. eg expression of MHC can be regarded as a phenotype. at the same time interaction of MHC with TCR which may result in a disease can also be regarded as a phenotype. if we carefully analyze the above mentioned example, both MHC expression and MHC-TCR interactions are entangled. this makes us to rethink the definition of phenotype.

3. Epigenitics have introduced gaps in or knowledge and understanding of genotype - phenotype relationships. eg transgenerational inheritance

4. epistasis and multi geneic traits are hard to detect even with the most advanced techniques in genomics such as sequencing. they play a major role in phenotype generation

check this paper to get an overview of why we cannot predict phenotype from a genotype alone.

http://www.ncbi.nlm.nih.gov/pubmed/22934970

various kinds of mutations results in disease such as indels, transposons, SNPs etc out of which SNP is the most abundant one in our genome. majority of diseases are multifactorial, which means that there are multiple causes at various magnitudes responsible for the disease phenotype. let us take SNP associations with diseases as an example. Association of SNPs are hard to detect due to linkage disequilibrium, epistasis, multi geneic interactions, population stratification etc..

especially SNPs with minor allele frequencies

Yes what you read about Phenotype is absolutely correct and the answers posted too.

Phenotype, Ha! a very complex trait to understand, vast research is going on....probably Phenome and Phenomics are latest subjects.

You have to correct yourself in the following "Genotype codes for Phenotype", that was a belief once upon a time. Now it is

Phenotype = Genotype + Environment + interaction of both G and E, go to Wikipedia you get excellent/useful and basic information or Google it.

Genetic heterogeneity is contrast to Pleiotrophy

I guess you know what is meant by genetic heterogeneity, in simple variety of genetic defects cause the same disease or

similar characters or a single phenotype or genetic disorder may be caused by multiple number of alleles.

"In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al." MeSH

When a single gene influences multiple phenotypes that is pleiotrophy eg. phenylketonuria

you find more information, if you are interested just go through

Closing the gap between genotype and phenotype

Peter K Gregersen volume 41 | number 9 | september 2009 | nature genetics

It’s the genotype, stupid!

http://onlinelibrary.wiley.com/doi/10.1111/j.1439-0388.2008.00795.x/pdf

There is a very good article in NRG it mentioned about GWAS limitations while focus on phenotypic influence of COMMON GENETIC VARIANTS

Review article NRG Vol.11, Nov.2010, 773-785, Bansal V et.al

Again, the correct equation is: phenotype = genotype + environment. The next part (+ interaction of both G and E) is an unnecessary redundancy, because it is already contained in the first part.

A little hint: Wikipedia is a very useful, but also very dangerous tool. The process of production of the various items is not equal to that of a “true” encyclopedia, and not totally guarantee the correctness of the information.

Returning to the question posed by Aamir Iqbal, there are at least three good candidates to explain the variability in the phenotype. First, the environment has a major role. Disease will not be expressed in persons with lactose or gluten intolerance if they are not exposed to lactose or gluten. Only a small proportion of persons who are homozygous for the common hemochromatosis mutation have overt disease, and the disease is less prevalent in women than in men, perhaps because of menstrual-blood loss, which limits iron accumulation.

A second factor is chance. Mutations causing disease are sometimes transmitted by completely healthy parents. Breast cancer does not develop in all female carriers of a BRCA1 mutation, and holoprosencephaly occurs in a only a minority of those with a mutation in the human sonic hedgehog gene (SHH), reflecting stochastic events as much as environmental or genetic factors that offer protection from or increase the risk of disease.

The third factor underlying phenotypic variability of inherited disease is genetic background. Modifier genes (genes that modify the clinical outcome of a genetic mutation) have been traditionally difficult to study, and most successes have come from the study of specific candidate genes that reside in the same biologic pathway or module as the disease gene itself (see Brunner HG. The variability of Genetic disease. N Engl J Med. 2012 Oct 4;367(14):1350-2).

I disagree with Fortunato's description as is an over-simplification of a complex matter. The correct equation is phenotype = genotype + environment + (genotype x environment) + error

Sorry, Tom, but I can not understand your answer completely. Could you explain better what do you mean by saying "genotype x environment", and the difference compared to "genotype + environment." Even the role of the error is not very clear.

Error is the stochastic variation associated with a particular observation of the phenotype (and is managed by use of replication and and appropriate experimental design). The phenotype is the result not only of the average effect of the differnt alleles at a given locus across test units and across environments, but is impacted by the interaction between the different alleles and the environments (including genetic backgrounds) in which they are evaluated. Phenotype is not simply the sum of the genotype effect and the environment effect, as indicated in the mathematical formula that you provide.

I am specifically referring to the use of multi-environment experiments (for example field trials) involving panels of progenies from bi-parental population(s) to generate phenotype data for use in mapping genomic regions contributing to the genetic control of the trait(s) of interest, which may themselves interact.

A not-so-recent reference that you may seek guidance from is

Yadav, R.S., F.R. Bidinger, C.T. Hash, Y.P. Yadav, O.P. Yadav, S.K. Bhatnagar, and C.J. Howarth. 2003. Mapping and characterization of QTL x E interactions for traits determining grain and stover yield in pearl millet. Theoretical and Applied Genetics 106:512–520.

Another example is the 2012 paper by Federer and Crossa: Walter T. Federer and José Crossa. 2012.. Screening experimental designs for quantitative trait loci, association mapping, genotype-by-environment Interaction, and other investigations. Front Physiol. 3: 156.

Other recent papers on the statistical models appropriate for multi-environment evaluation of large panels of entries for mapping of, for example, drought tolerance of grain yield, have been published by a Generation Challenge Program-supported team at Wageningen.

Please let me know if you need any further clarification.

Best regards,

Tom

Tom, thank you for your excellent answer, but I still think that "my" simplified formula contains well everything you've said. When I say that the phenotype is the result of "genotype + environment" I mean exactly that what we observe is not simply the result of the action of the genotype, but rather it is the result of complex interactions between phenotype and environment, and it is obviously not an algebraic sum.

Sorry -- it seems we'll need to agree to disagree. The statistical analysis required to measure genotype x environment interaction is considerably more complicated than the simplistic explanation that you offer and without this, we cannot generate the numbers required to measure the importance (and possible statistical significance) of the interaction between genotype and environment in determining phenotype.

Tom, it's always a pleasure to talk to you about such an important topic.

I only regret not being able to explain a very simple concept. The formula proposed by me (which incidentally is the same as thousands of teachers use to teach genetics to millions of students around the world) is not a mathematical formula, but just a way to briefly describe (in a simple but not simplistic way) the concept that the phenotype we observe is not simply the result of the expression of the genotype or of the action of the environment, but rather the result of a complex interaction between these two factors (genotype and environment). So this formula has absolutely no claim to generate numbers, as you thought (but how could it?).

I believe that you will remain in your opinion, but it comforts me to know that in the world there are millions of people who have in mind the same concept that I have in mine.

Hi! Fortunato,

Kindly do not think that I am pointing out as the discussion is going on I am writing this.

I mentioned the following in beginning

"Phenotype = Genotype + Environment + interaction of both G and E"

then you mentioned "phenotype = genotype + environment. The next part (+ interaction of both G and E) is an unnecessary redundancy, because it is already contained in the first part."

Now you are saying the same "but rather the result of a complex interaction between these two factors (genotype and environment)",

Of course phenotype is very complicate issue and always debatable subject. Dr. Maheswaran M, Plant Breeder says that phenotype is a dynamic character always under change even you measure thousand replicates it does not give the same measure. It is a polygenic (Quantitative) trait under the control of several genes. Phenotype keeps on "changing it expression across the environments and genetic backgrounds". Even biometrical tools could not resolve the accuracy of Phenotype. Molecular markers could locate the loci to some extent with major or minor effects.

Ref. M. Maheswaran. Mapping Quantitative Trait Loci in Plants: Approaches and Applications. Bioinformatics and Statistical Genomics.

Hi Jetty,

I finally agree with you. Thank you for your contribution to the discussion.

A particular geneotype does not necessarily guarantee a particular phenotype. Understanding what factors can change this expression is quite complex.. What is what i believe that above statement meant.