Hi Snijesh,

the chance is weak but possible. since lot of genes are involved in many pathways, a particular variant can have various effects depending of the genome status of the patients (I mean that this variant can be associated with other variants in interacting other genes to induce changes in so many pathways). as you can understand, it's very complex and more complex is to test all variants and their impact on pathways.

for your question, yes it's possible.

fred

Yes, genetic redundancy will have an effect. If the gene has two functions, both of which are redundant compared to another gene, then mutating the gene will have different effects depending on whether the redundant pairs are mutated or not.

Hi there, I agree with both Emily and Frederic, even if I am weaker in proteomics, bio-pathways and functional genomics than the probability of such a family. Moreover I should involve possible modifiers, which can segregate in a complex manner.

Thank You ...Frederic Lepretre, Emily Perry, Ján Miertuš, Sophie Limou

Through literature reviews I have found the same that you all have mentioned. But, I have some more questions here,

1. If a mutated gene is causing multiple diseases how is personalized medicine based on genomics possible?

2. How is early detection of a particular disease possible based on genomic profile?

Hi Snijesh,

good questions, indeed, hard to answer.

1. first, it's not because you've got mutated genes that you'll develop some disease, since most of them are multifactorial. changing life styles in particular genomics could avoid complications, but not sure.

2. coming from the first question/answer, causes of some diseases can be too complex. recording the familial history and genomics could be some help.

in return I've got one question, which precise disease you're interested in?

fred

For the infective diseases like the malaria,it is important whether they can be prevented.

The children (boys) who are carriers of the hypofunctional variants of the G6PD gene and prone to develop nonspherocytic hemolytic anemia, are left at risk of the hemolytic crisis even at taking the low doses of drugs advised for malaria prevention

Hi Frederic,

I am working on early breast cancer prediction based on genomic profile. The germline mutations of genes like BRCA1, BRCA2 and BRIP1 are well known for breast cancer detection. But, I am focusing on  both Somatic and Germline mutation. So, if I find some frequently mutated genes in breast cancer, how accurate will it be to convey a patient that you are at high risk or not for breast cancer?

A snapshot of the workflow is attached. Please let me know your suggestions

Hi Andrzej Pawlak,

Can you be more specific to my question?. I am sorry, I did not get your point

Thank You

Hey Snijjesh VP

For Your question concerning "can it"? answer is: Yes it can

Andrzej Pawlak

Yes, mutations in the same gene (regardless of region) can lead to different traits.

An example from Cancer is the classic tumor suppressor BRCA2.

A truncating mutation in BRCA2 can lead to :

1. Breast Cancer

2. Ovarian Cancer

3. Pancreas Cancer

4. Prostate Cancer

5. and other cancers, where the phenotype is not strongly reported yet.

Another example is the telomerase gene, telomerase reverse transcriptase (TERT)–CLPTM1-like (CLPTM1L) locus influences risk for glioma, bladder and lung cancers

This phenomenon is called pleiotropy

Suggested Reading:

doi:10.1038/nrg3461

https://www.khanacademy.org/science/biology/classical-genetics/variations-on-mendelian-genetics/a/pleiotropy-lethal-alleles-and-sex-linkage

To finally address your specific question.

The phenotype is not purely determined by the genotype. Infact, phenotype:genotype correlation is one of the hardest part about disease genetics. So, an absolute  risk estimation is not possible without knowing competing risks such as age, gender, ethnicity, There are some calculators available for the most common diseases.

EDIT: Since, I saw your explanation in another follow up post on breast cancer, I also recommend you to read our new paper in JAMA.

You can see the correlations are not as hard and fast as people will have you believe.

doi: 10.1001/jama.2017.11137

Yes, pleiotropy is universal. A gene can affect multiple traits just as a polygenic trait is affected by many genes. A famous geneticist (I don't recall his name) stated years ago that each gene affects every trait and each trait is affected by every gene. A phenotype is strictly a constellation of many traits. Studying a trait in isolation is at best an approximation.

I think the best example is FGFR3. Mutations in this gene can cause a variety of skeletal dysplasias: hypochondroplasia, achondroplasia, the lethal thanatophoric dysplasias,  SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), Muenke coronal craniosynostosis and Crouzon syndrome with acanthosis nigricans. Even different amino acid substitutions on the same position can cause different phenotypes. "Recent evidence suggests that the phenotypic differences may be due to specific alleles with varying degrees of ligand-independent activation, allowing the receptor to be constitutively active" (Vajo et al. 200). 

This paper below has a great review of this gene and a good summary of the FGFR3 mutations and different diseases associated.

Article The Molecular and Genetic Basis of Fibroblast Growth Factor ...

Hi, Daniela Hartstern,

Thank you. Very valuable information

1. If a mutated gene is causing multiple diseases how is personalized medicine based on genomics possible?

2. How is early detection of a particular disease possible based on genomic profile?