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What does this mean?

If someone could care to explain to me what the following paragraph means, especially the sentences near the end that would be highly appreciated!

While PGD is available for a large number of single-gene and chromosomal disorders,
there are a few cases in which selection of unaffected embryos using PGD would not be possible
and effective, that is, where no embryos from a given couple are unaffected. In these
exceptional cases, genome editing might offer an alternative approach. They include:
where there are Y chromosome defects
eliminating or perhaps correcting mutated mitochondrial DNA
dominant genetic disease (e.g. late onset, such as Huntington’s or Alzheimer’s disease, or
breast cancer) where one parent is homozygous (100% risk to the offspring) or both parents
are heterozygous (75% risk)
recessive genetic disease where both parents are homozygous (100% risk) or one parent
homozygous, one heterozygous (50% risk)
inversions and deletions of chromosome segments
where there are no suitable, unaffected embryos available for transfer, for example where
multiple, independently assorting, traits are sought (as in the case where one wants to select
an embryo with both a particular disease-related genotype and a specific HLA tissue type). While these exceptions may be very limited, it is possible to imagine that advances in the allied
technology of whole genome DNA sequencing will increase the detection of gene variants or
combinations of variants that may be associated with heightened disease risk. If developments in
personalised genomic medicine drive the identification of such disease-predisposing variants, it
is likely there will be pressure to apply this knowledge to embryos. Indeed, if less severe or
penetrant conditions are brought into consideration, it will be highly unlikely that any embryo will
be free of every risk-associated variant.
Original post by esmeralda123
If someone could care to explain to me what the following paragraph means, especially the sentences near the end that would be highly appreciated!

While PGD is available for a large number of single-gene and chromosomal disorders,
there are a few cases in which selection of unaffected embryos using PGD would not be possible
and effective, that is, where no embryos from a given couple are unaffected. In these
exceptional cases, genome editing might offer an alternative approach. They include:
where there are Y chromosome defects
eliminating or perhaps correcting mutated mitochondrial DNA
dominant genetic disease (e.g. late onset, such as Huntington’s or Alzheimer’s disease, or
breast cancer) where one parent is homozygous (100% risk to the offspring) or both parents
are heterozygous (75% risk)
recessive genetic disease where both parents are homozygous (100% risk) or one parent
homozygous, one heterozygous (50% risk)
inversions and deletions of chromosome segments
where there are no suitable, unaffected embryos available for transfer, for example where
multiple, independently assorting, traits are sought (as in the case where one wants to select
an embryo with both a particular disease-related genotype and a specific HLA tissue type). While these exceptions may be very limited, it is possible to imagine that advances in the allied
technology of whole genome DNA sequencing will increase the detection of gene variants or
combinations of variants that may be associated with heightened disease risk. If developments in
personalised genomic medicine drive the identification of such disease-predisposing variants, it
is likely there will be pressure to apply this knowledge to embryos. Indeed, if less severe or
penetrant conditions are brought into consideration, it will be highly unlikely that any embryo will
be free of every risk-associated variant.

Not my field at all, but here is how I read it from a common-sense pov.

The bullet points are situations where PGD will not help you select an embryo for implantation because these are all examples where all embryos might be affected by the unwanted condition or where it is a complex, multi-locus condition like the HLA profile. (for example, all embryos will be affected by a dominant disorder if one parent is homozygous for that disorder; mitochondria are inherited from the mother only, so if she has a mitochondrial DNA disorder, all the embryos will have it too). So there's no point doing the procedure in these situations.

The last para (from "While these exceptions..." on) points out that PGD is only practical for embryo selection when you are looking for disorders which are the result of single gene defects, or simple chromosome differences such as sex determination. If the defects are caused by more complex genetic interactions - for example, they occur only when a particular combination of several alleles is present - then techniques like whole genome sequencing will be necessary to detect those embryos which are at high risk.

The last sentences suggest that as medical technology extends to analysing the genome of every individual to identify what particular vulnerabilities or risks each one of us has (even for less severe, chronic conditions like heart disease or late onset cancers), then we would expect people wil want to do the same for embryos. Does that sound right?

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