Viability Primary Screen IMPC_VIA_002

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Purpose

To assess the postnatal viability, sub-viability, and lethality of mice of each zygosity and sex during cohort production.

Experimental Design

  • Monitor genotypes of at least 28 live offspring from a specified breeding strategy (e.g. HetXHet, HetXHom). A single breeding strategy should be used per procedure so that totals of pups can be grouped together. If another breeding strategy is used for some litters, please submit a separate procedure, distinguished by sequence id. Record the genotypes of as many live pups as possible; P-values will be deflated by increased numbers of pups, allowing more specific calls to be made.
  • Record age of pups at genotype (P1-P28)
  • (Optional) Record the age of the youngest and oldest female parents when cohort breeding starts.
  • Record raw numbers of live pups of each sex/zygosity combination.
  • Identify viability/subviability/lethality of zygosities/sexes by application of a statistical test and P-value threshold. Centres might also apply hard rules (less than 50% of expected pups) to determine whether to put a particular zygosity through the adult pipeline or embryo pipeline.

Procedure

  1. Determine gene category (see Notes below).
  2. Select breeding strategy to generate phenotyping cohort for a colony.
  3. Genotype all live pups and record numbers of each sex/zygosity. If possible, record pups grouped by litter, along with the parental IDs and date of birth for each litter. Record all three parents for trio matings. Where litter data is not available, group these pups together as the “noLitter” group.
  4. Continue to record genotypes of pups for as long as possible. There is no hard minimum limit on numbers, but P-values are more likely to reach significance with greater numbers, and therefore more granular/specific calls can be made (see Notes below).
  5. Submit numbers to seriesParameters. Include zeros for all categories where no pups were recorded, even if they were not expected e.g. WTs from a HetXHom mating. Do not submit values to the derived total or outcome parameters (see example submission file).
    1. Where litter data is available, submit each litter as a single increment of all “Number of…” parameters. Include parental IDs and dates of birth where possible. Use a unique identifier for each litter as the incrementValue. Trios matings are indicated by the presence of a second female parentID; otherwise, omit this ID.
    2. Where litter data is not available, submit pups grouped together as a single increment of all “Number of…” parameters, using incrementValue=”noLitter”. Omit the litter date of birth for this group. “unknown” can be submitted for parentalIDs for this group (or any litter where the parent cannot be identified).
  6. Where a particular zygosity is identified as lethal (or severely subviable), an alternative may be put through the adult phenotyping pipeline e.g. in the case of homozygous lethality, heterozygotes can be phenotyped.

Notes

Anzygous is a term to describe the zygosity of a female animal for a gene on the Y-chromosome i.e. no copies of the gene expected. As with all sex/zygosity categories, please report zeros for all litters/colonies where no animals of this type were found, even if they were not expected from that breeding strategy.

Gene category should be available from production labs at each centre. It can be ascertained for most genes by searching NCBI gene. Any gene on a numbered chromosome is autosomal. Genes at the distal tips of the X or Y chromosomes might be pseudoautosomal, rather than X-chr or Y-chr. Contact production labs or DCC data wranglers for assistance.

Parameters & Metadata

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Name Version Type Description Req. Upload Req. Analysis Annotation Increment Options Ontology Options Unit Data Type Derived History Key Group
Name Version Type Description Req. Upload Req. Analysis Annotation Increment Option Ontology Options Unit Data Type Derived History Key Group