Any geneticists out there?

[Undertown]

When I was a child in the 1970s my family were asked to give blood for some medical research by University College London. It was something to do with a rare enzyme I think and also something about chromosome 22. I guess this was all quite early in the field of genetics? I have the letter with the results but it makes no sense to me and I’d really like to know what it was about. They also sent a paper which is presumably related with the title “genetically determined electrophoretic variants of human red cell NADH diaphorase” but it’s beyond my comprehension. Is there anyone with expertise in this field who’d be willing to have a look at the letter for me and explain it in laymen’s terms? Bit of a long shot I know but I thought I’d ask.

I am a geneticist. Happy to have a look at the letter and paper if you want to message me..

Nadh is an enzyme which is in our livers which breaks down alcohol so I would guess the research was looking at changes in the nadh gene in different people to see if there were any differences in the gene which then made the nadh work less well or better.

NADH is found in every cell, not just the liver. It is a fundamental electron carrier in cell metabolism across the entire phylogenetic tree. NADH diaphorase is important in transporting electrons between oxidized and reduced forms of NADH. Differences in its ability to carry out that function will have wide ranging effects on cell metabolism and overall health.
Electrophoretic variants means that they ran a sample of NADH molecules on (presumably) an acrylamid gel to separate out different variants (based on their isoelectric point which changes due to genetic differences in amino acid sequence) and then assessed their ability to reduce/oxidize some substance, most likely a dye. They will have compared that to various controls, like fully functioning NADH diaphorases and ones with known defects.

I'm a molecular biologist/biochemist, not a geneticist, but might be able to decipher some of your results. BTW I've looked up your paper and it is from 1970 (which makes sense, as nobody has looked at electrophoretic variants of proteins for about 30 years - these days we would know the precise amino acid sequence of each variant). I have just downloaded a PDF of it (looks so adorably old-fashioned!) will have a read during my coffee break.

Thanks for the offers. Really appreciate it. I’ve realised I can’t share images on private messages so I’ve anonymised the two letters and will post the below. For context, Mr & Mrs E are my parents. Their children are PE, JE, GE and SE ( I’m SE). RC is Mrs E’s mother, HB is Mrs E’s sister. Hope it’s readable.

@Undertown How does the sentence after "inherited along..." finish? It's in the middle of the first longer paragraph. I can't read that.

Are your family of Eastern Asian descent by any chance?

…along with the gene for secretion or non secretion of substances in the saliva.

No. Very white british for generations. Did an ancestry dna test and was quite disappointed!

The 1970 paper says that the Dia 3-1 variant was found only once in a sample of 1975 English individuals, and once again in a sample of 254 black individuals. None in other ethnic groups.

Which explains why the researchers were so interested in finding more individuals with such a rare variant and investigating the inheritance.

It could have been a new or recent mutation. I wonder if there is now whole genome data that gives us a better idea about its frequency.
1970 was really early with respect to genetics. It's seven years before Carl Woese first published using gene sequences (of 16S and 18S rRNA genes) for making phylogenetic trees. The changes on molecular biology and genetics and the technological advances in the past 3-4 decades are mind boggling.

It took some searching, but I believe what we're looking for in current terminology is cytochrome b5 reductase 3, which is located on Chromosome 22.

https://www.ncbi.nlm.nih.gov/gene/1727

That’s very pretty! Have I got one of those? (Non scientist here!!)😃

You do indeed!