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BLD460 Michigan State University HLA Writing Paper

BLD460 Michigan State University HLA Writing Paper

Question Description

This week will be a bit different. Different format and different assessment. The focus is on DNA based typing as it applies to the HLA/Tissue Typing Laboratory.

There are a series of articles for you to read. In these articles, there is the reference to methods you are very familiar with: SSP, SSO, Hybridization, Sequencing by capillary and next-generation sequencing. There is the reference to HLA, STR’s, engraftment, disease associations and pharmacogenetics. All topics that have been covered here or in other courses you have taken (430, 434, 435 and likely others. It will be up to you to refresh yourself on these topics before, during and after reading the articles so that you place put them into proper context.

I think you can appreciate that HLA typing is a daunting task. Roughly 20,000 different alleles to discriminate and come up with a type that can be used for proper matching of donors and recipients. Furthermore, HLA typing is used for the selection of platelets and also performed to rule in/rule out disease associations. It can also be used as a companion diagnostic for some therapeutic/pharmaceutical decisions. The typing can be done at a lower/single field resolution or higher depending upon needs. It is well established that low resolution works well for solid organ transplant decisions and higher two fields (or more) is needed for bone marrow/hematopoietic stem cell transplants. Also, keep in mind that when you are dealing with deceased donors, you have to have HLA typing done in a matter of hours. Disease association and pharmacogenetics often need higher resolutions also. With the higher level of HLA antibody characterization in practice, higher resolution is sometimes needed in solid organ decision making when there are allelic specific antibodies present.

Engraftment is an arena unto its own. It is not really typing per se but an exercise in defining differences between donor and recipient and then establishing an extreme level of sensitivity of detection. The documentation of sensitivity is a key point when validating the assay.

Several of the articles discuss “next-generation sequencing,”something you should be familiar with from previous lessons but clearly a platform that the “HLA lab” is adopting. Please make sure you review your previous lessons so that you can overlay the practicality of how this adaption/adoption is can progress.

Now for the assessment:

This assessment is somewhat of fantasy/dream sequence (no pun intended) for you. For some, this may soon be a reality as you will be entering the workforce.

Let’s assume you have been working for a few years in an HLA lab that supports solid organ (deceased and living donors) and bone marrow transplants as well as disease association and engraftment. Your boss (lab director) sends you to a professional meeting where most of the talks discuss the emergence of NGS into your field and how vital is because it brings a new level of effectiveness to how your lab results are influences patient outcomes. You also spend time in the vendor exhibit that has multiple manufacturers of NGS platforms and you speak with your peers at these booths and learn how this technology could fit into your lab. You return from the meeting, and your boss asks: “What did you learn and how can it apply to us?”. You reply: “We need to move into NGS to stay current and relevant to our clients?”. Your boss replies: “Provide me an executive summary to support that comment”?.

You need to comply with a document that is not more than 750 words to support how NGS can be used in this lab and also, what older technologies that you need to maintain. Use the articles to support your conclusions. Keep in mind that in order to support the transition to the new technology there need to be persuasive reasons such as cost, sensitivity, better allele detection coverage, turn-around-time, less need for additional testing, less technologist time involvement, something that makes the switch a better choice for the lab.

If you are not familiar with what an executive summary comprises, it is a short, 1 page or less document that has all the salient points of the larger document behind it. It is a condensed summary that allows someone to refer to when presenting or it has the points that would make the reviewer look into the larger document because a good case is made. It has facts and data in it, but short and to the point.

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