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Genetic Carrier Screening Test

Hello, dear community,

I am researching a method to perform a genetic carrier screening test.

So far, I have two exomes, from two future parents. I processed the fastq files with GATK best practices and the annotation was done with ANNOVAR.

I only have two subjects, the fututure mother and father.

I want to compute the probability of each variant in the exome of being inherited to the child. Also, I want the inheritance pattern, i.e Dominant, Recessive, X-linked, etc..

The problems comes because there is not enough literature to have a data base to provide such information, i.e the inheritance pattern.

However, I reached with two possible methods, MAPPIN and MAVERICK. But, I do have problems when running. They do not work. Is there any other method ?

My goal, is when I have the probability of being recessive or dominant, joint these two probabilities, in order to get the desired result.

Or do you have any suggestions to carry out these genetic test ? Is any package in bioconductor ?

Kind regards

Edmond

annovar mappin vep maverick
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updated by LChart LChart • written by Edmond • Edmond

1 answer

Edmond-

OMIM contains information on inheritance patterns of mendelian traits (which really means, the inheritance patterns of most alleles that arise that confer the trait), and the genes that have been mutated to confer the trait. ClinVar contains information on reported alleles linked (or likely linked) to traits.

A simple pre-conception screen might be:

  1. Annotate exomes with functional impact and ClinVar
  2. Flag any variants already in ClinVar as likely pathogenic or pathogenic (not very likely to happen, but it could)
  3. Flag any loss-of-function variants in OMIM-provided genes, and annotate with inheritance pattern of corresponding trait

It should also be pointed out that you can ignore (and should filter out) any dominant trait not present in the parents.

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written by LChart LChart

But the problem is that not all variants are now known the mode of inheritance

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written by Edmond • Edmond

For the most part yes, yes you do. ClinVar links functionally-typed variants (missense, nonsense, both, or neither) to traits; OMIM links traits to modes of inheritance. You should be able to reason out how to link the inheritance of a specific variant to a that of a trait.

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