Checking Your Carrier Status for Genetic Diseases

The term “carrier status” when applied to a genetic disease usually means looking at whether or not you are heterozygous (have one copy) for a mutation that causes a Mendelian genetic disease. Generally, these are the rare diseases that you would need two copies of the variant to have the disease.

Take cystic fibrosis as an example…  the Cystic Fibrosis Foundation explains that “People with CF have inherited two copies of the defective CF gene — one copy from each parent.  Both parents must have at least one copy of the defective gene.  People with only one copy of the defective CF gene are called carriers, but they do not have the disease.”

A word of caution before you go any further!  While genetic information from 23andMe or a similar DNA test is generally accurate, always re-confirm with a clinical test before making a major health decision.  Also, the information from studies that I’ve listed below could be inaccurate or have changed since the article was published. Check and double check before you do anything with the information below. There are several different companies that do genetic testing and counseling if you are looking for information before having a baby.

It is also important to know that researchers are discovering new things all the time about rare genetic diseases, such as this Nature article that looked at over 500,000 people’s genes and found that there are people have that have a mutation for a genetic disease without symptoms.  This is a fairly new science, and researchers are still making discoveries all the time.

So with all the caveats above, why even look into your carrier status for genetic diseases? If you have kids already, it may be important to let them know if they are possibly a carrier for a genetic disease. Others in your family may also be affected.

For most of the diseases listed below, being a carrier generally means you are not affected by the disease, but for some diseases, it is possible to be mildly affected. In general, when someone is heterozygous, the normal, healthy allele (version from one parent) can compensate for the allele (version from the other parent) that isn’t working. But take hemochromatosis as an example– it is possible for someone who is heterozygous to have issues with iron overload, and men especially should keep an eye on their iron levels.

For more information on inheritance, www.yourgenome.org has a nice explanation.

The list below is in no way complete and is for informational purposes only.  23andMe data only covers a small percentage (less than 1%) of your genome, and this is just a list of SNPs that I’ve compiled along the way.  I highly suggest putting them into an Excel file as an easy way to see your data.  Some of these are also on the 23andMe health report if you have purchased that, but there are several listed below that aren’t included in their reports.  All of the information can also be found on SNPedia.com.

Thinking that it is not worth your time to look at rare diseases?  If you consider that there are more than 7,000 rare diseases and that they affect 1 in 10 people in the US, it really isn’t out of the realm of possibility to be a carrier or affected by a rare disease.  Learn more at Global Genes or the National Organization for Rare Disorders.

If you know of other SNPs to add to this list, please add them in the comments below.

Note that all of the risk alleles are listed in the FWD orientation to match with your results on 23andMe or AncestryDNA. If you are using data from another source, you should check to see if it is all listed in the FWD orientation.

Condition Gene SNP Risk Allele (fwd) Notes/References
Agenesis of the Corpus Callosum with Peripheral Neuropathy SLC12A6 i5012573 D rs515726215  more
Agenesis of the Corpus Callosum with Peripheral Neuropathy SLC12A6 i5012575 A
Alpha-1 Antitrypsin Deficiency SERPINA1 rs17580 A Homozygous has 60% of normal enzyme function.   More of a problem in conjunction with another variant.  more… 
Alpha-1 Antitrypsin Deficiency SERPINA1 rs28929474 T Homozygous usually leads to severe alpha-1-antitrypsin deficiency. Heterozygous may also have an increased rate of lung or liver problems. more
Argininosuccinate lyase deficiency ASL rs28941472 G There is both a neonatal form and a late-onset form more
Argininosuccinate lyase deficiency ASL rs201523601 T
Autosomal recessive spastic ataxia of Charlevoix-Saguenay SA/CS i5012578 D rs281865117, more
Autosomal Recessive Polycystic Kidney Disease PKHD1 i5000043 G rs200511261,  (huge list)
Autosomal Recessive Polycystic Kidney Disease PKHD1 i6016630 T rs794727819, classified as likely pathogenic
Autosomal Recessive Polycystic Kidney Disease PKHD1 i5007345 G rs137852948
Autosomal Recessive Polycystic Kidney Disease PKHD1 i5000045 G rs760222236, i6016633
Autosomal Recessive Polycystic Kidney Disease PKHD1 i5000047 C rs369925690
Autosomal Recessive Polycystic Kidney Disease PKHD1 i5012610 D rs398124502
Autosomal Recessive Polycystic Kidney Disease PKHD1 i5000042 G rs137582950
Autosomal Recessive Polycystic Kidney Disease PKHD1 i5012612 A rs137852949
Autosomal Recessive Polycystic Kidney Disease PKHD1 rs28939383 A rs28939383
Beta Thalassemia HBB rs11549407 A  Heterozygous variants can cause a milder form of the disease. more…
Bardet-Biedl Syndrome MKKS rs28937875 T more
Bardet-Biedl Syndrome BBS10 rs148374859 C
Bardet-Biedl Syndrome BBS12 rs121918327 T
Bardet-Biedl Syndrome BBS1 rs113624356 G
Bardet-Biedl Syndrome BBS1 rs35520756 A Though this one is listed as pathogenic, it is fairly common and looks to only add risk with other variants.
Beta Thalassemia / Sickle Cell Anemia HBB i3003137 A rs334, homozygous A/A is pathogenic for sickle cell anemia, heterozygous leads to reduced risk of malaria
Beta Thalassemia HBB rs33915217 G
Beta Thalassemia HBB rs33944208 T
Beta Thalassemia HBB rs33960103 G
Beta Thalassemia HBB rs33971440 T
Beta Thalassemia HBB rs33985472 C
Beta Thalassemia HBB rs33986703 G
Beta Thalassemia HBB rs34451549 A
Beta Thalassemia HBB rs34598529 C
Beta Thalassemia HBB rs34690599 C
Beta Thalassemia HBB rs35004220 T
Beta Thalassemia HBB rs35724775 G  read more
Beta Thalassemia HBB rs63750783 T
Bloom’s Syndrome BLM i4000396 I rs113993962
Canavan Disease ASPA rs28940279 C read more
Canavan Disease ASPA rs28940574 A
Congenital Disorder of Glycosylation Type 1a PMM2 i5012679 A read more
Congenital Disorder of Glycosylation Type 1d PMM2 rs28940588 T
Congenital Disorder of Glycosylation Type 1a PMM2 i5012680 A rs28936415
Connexin 26-Related Nonsyndromic Sensorineural Hearing Loss GJB2 i4000434 D rs80338939
Connexin 26-Related Nonsyndromic Sensorineural Hearing Loss GJB2 rs72474224 T may cause only mild hearing loss in some populations
Connexin 26-Related Nonsyndromic Sensorineural Hearing Loss GJB2 i4000435 D rs80338942
Cystic Fibrosis C/TFR i3000001 D rs11399360, the most common cause of cystic fibrosis
Cystic Fibrosis C/TFR rs75961395 A more…
Cystic Fibrosis C/TFR rs78655421 A
Cystic Fibrosis C/TFR rs121909011 T
Cystic Fibrosis C/TFR i4000297 A
Cystic Fibrosis C/TFR i4000291 A
Cystic Fibrosis C/TFR i4000299 T
Cystic Fibrosis C/TFR rs113993959 T
Cystic Fibrosis C/TFR i4000301 A
Cystic Fibrosis C/TFR rs75527207 A i4000305
Cystic Fibrosis C/TFR i4000306 T
Cystic Fibrosis C/TFR i4000307 C
Cystic Fibrosis C/TFR i4000308 T
Cystic Fibrosis C/TFR i4000309 A
Cystic Fibrosis C/TFR i4000311 G
Cystic Fibrosis C/TFR i4000313 D
Cystic Fibrosis C/TFR i4000314 T
Cystic Fibrosis C/TFR rs77188391 T i4000315
Cystic Fibrosis C/TFR i4000316 D
Cystic Fibrosis C/TFR rs76713772 A i4000317
Cystic Fibrosis C/TFR i4000318 A
Cystic Fibrosis C/TFR i4000319 D
Cystic Fibrosis C/TFR rs80224560 A i4000320
Cystic Fibrosis C/TFR rs75096551 A i4000321
Cystic Fibrosis C/TFR i4000322 D
Cystic Fibrosis C/TFR i4000323 D
Cystic Fibrosis C/TFR i4000324 I
Cystic Fibrosis C/TFR rs75039782 T i4000325
D-Bifunctional Protein Deficiency HSD17B4 i5007145 A Heterozygous carriers may also have problems with the breakdown of fatty acids.
D-Bifunctional Protein Deficiency HSD17B4 i5007146 T
Deglycosylation Disorder NGLY1 rs201337954 A
Denys-Drash syndrome WT1 rs28941778 T
Dihydrolipoamide Dehydrogenase Deficiency DLD DLD i5003700 T more
Factor VIII Deficiency – Hemophilia F8 rs28933681 T
Factor VIII Deficiency – Hemophilia F8 rs28933679 C
Factor IX – Hemophilia F9 i5007022 G Very rare (possibly extinct) form of Hemophilia
Factor XI Deficiency – Hemophilia F11 i4000397 A
Factor XI Deficiency – Hemophilia F11 rs121965063 T i4000398
Factor XI Deficiency – Hemophilia F11 rs121965064 C i4000399
Familial Dysautonomia IKBKAP rs111033171 G i4000334
Familial Dysautonomia IKBKAP i4000400 G
Familial Hypercholesterolemia Type B APOB rs144467873 A i4000339
Familial Hypercholesterolemia Type B APOB rs12713559 A
Familial Hypercholesterolemia Type B APOB rs5742904 T
Fanconi Anemia FANC/C rs104886456 A i4000336
Fanconi Anemia FANC/C rs104886457 A i4000412
Fanconi Anemia FANC/C i4000413 D
Gaucher Disease GBA rs421016 G
Gaucher Disease GBA rs80356773 T i4000386
Gaucher Disease GBA i4000415 C rs76763715
Gaucher Disease GBA i4000417 I rs387906315
Gaucher Disease GBA i4000419 A rs80356769
Glutaric Aciduria GCDH rs121434369 T
Glycogen Storage Disease Type 1a G6PC rs1801175 T i3002486
Gracile Syndrome BCS1L rs28937590 G i5012660
Hemochromatosis HFE rs1800562 A Known as C282Y.
Hemochromatosis HFE rs1799945 G Known as H63D, can cause milder form of hemochromatosis or when combined with rs1800562
Hemochromatosis HFE rs1800730 T Known as s65C, possible causes milder form of hemochromatosis
Hereditary Fructose Intolerance ALDOB i5012664 C rs78340951
Hereditary Fructose Intolerance ALDOB i5012665 D
Hereditary Fructose Intolerance ALDOB rs76917243 T
Hereditary Fructose Intolerance ALDOB rs1800546 G
Kindler Syndrome FERMT1 rs121918293 A
LAMB3-Related Junctional Epidermolysis Bullosa LAMB3 i5012669 A rs80356680
LAMB3-Related Junctional Epidermolysis Bullosa LAMB3 i5012671 A rs80356681
LAMB3-Related Junctional Epidermolysis Bullosa LAMB3 i5012672 A rs80356682
Limb-girdle Muscular Dystrophy SGCA rs28933693 T
Limb-girdle Muscular Dystrophy SGCB rs28936383 C
Limb-girdle Muscular Dystrophy FKRP rs28937900 A
Maple Syrup Urine Disease Type 1B BCDKDHB i3002808 C more
Maple Syrup Urine Disease Type 1B BCDKDHB i4000422 A Known as G278S
Medium-Chain Acyl-CoA Dehydrogenase Deficiency A/CADM rs121434282 C i5003116
Medium-Chain Acyl-CoA Dehydrogenase Deficiency A/CADM rs121434281 T i5003117
Medium-Chain Acyl-CoA Dehydrogenase Deficiency A/CADM i5012755 T
Medium-Chain Acyl-CoA Dehydrogenase Deficiency A/CADM rs121434280 C
Medium-Chain Acyl-CoA Dehydrogenase Deficiency A/CADM rs77931234 G
Medium-Chain Acyl-CoA Dehydrogenase Deficiency A/CADM i5012760 T rs373712782
Medium-Chain Acyl-CoA Dehydrogenase Deficiency A/CADM rs121434274 A
Mucolipidosis IV MCOLN1 rs104886461 G i4000425
Mucolipidosis IIIa GNPTAB rs34159654 C pseudo-hurler polydystrophy
Neuronal Ceroid Lipofuscinosis CLN5 i5012678 D rs386833969
Neuronal Ceroid Lipofuscinosis PPT1 i5012622 G more
Neuronal Ceroid Lipofuscinosis PPT1 rs137852695 A
Neuronal Ceroid Lipofuscinosis PPT1 i5012624 A
Niemann-Pick Disease Type A i4000381 C more…
Niemann-Pick Disease Type A i4000383 D
Niemann-Pick Disease Type A rs120074117 T
Nijmegen Breakage Syndrome NBN i5012770 D
Pendred Syndrome SLC26A4 rs121908362 G hearing loss
Pendred Syndrome SLC26A4 rs111033244 G
Pendred Syndrome SLC26A4 rs111033199 T
Pendred Syndrome SLC26A4 i5000696 G
Pendred Syndrome SLC26A4 i5012616 C
Pendred Syndrome SLC26A4 i5012618 C
Phenylketonuria PAH rs5030843 A more…
Phenylketonuria PAH rs5030846 T
Phenylketonuria PAH rs5030847 A
Phenylketonuria PAH rs5030850 A
Phenylketonuria PAH i3003401 A rs5030851
Phenylketonuria PAH rs5030856 C
Phenylketonuria PAH rs5030859 T
Phenylketonuria PAH rs5030860 C
Phenylketonuria PAH i4000467 A
Phenylketonuria PAH i4000470 C
Phenylketonuria PAH rs75193786 G
Phenylketonuria PAH rs76296470 A
Phenylketonuria PAH rs62642932 T
Phenylketonuria PAH rs62642933 C
Phenylketonuria PAH rs62516092 C
Phenylketonuria PAH rs62514953 T
Phenylketonuria PAH i4000478 T
Phenylketonuria PAH i4000479 C
Phenylketonuria PAH rs62508588 T
Phenylketonuria PAH rs28934899 G
Phenylketonuria PAH rs5030841 G
Phenylketonuria PAH rs5030849 T
Phenylketonuria PAH rs5030852 A
Phenylketonuria PAH rs5030853 A
Phenylketonuria PAH rs5030855 T
Phenylketonuria PAH rs5030857 A
Phenylketonuria PAH rs5030858 A
Phenylketonuria PAH rs5030861 T
Primary Hyperoxaluria Type 2 GRHPR i5012628 D rs80356708
Primary Hyperoxaluria Type 3 GRHPR i5012629 D rs180177309
Rhizomelic Chondrodysplasia Punctata PEX7 rs61753238 G more…
Rhizomelic Chondrodysplasia Punctata PEX7 rs1805137 A
Salla Disease SLC17A5 i5012634 A
Sjogren-Larsson Syndrome ALDH3A2 rs72547571 T
Tay-Sachs Disease HEXA i4000391 I
Tay-Sachs Disease HEXA rs147324677 T
Tay-Sachs Disease HEXA rs121907954 T
Tay-Sachs Disease HEXA rs76173977 T
Torsion Dystonia TOR1A i4000446 D deltaE302
T/TR-Related Cardiac Amyloidosis T/TR rs76992529 A more…
T/TR-Related Familial Amyloid Polyneuropathy T/TR i3002758 A rs28933979
T/TR-Related Familial Amyloid Polyneuropathy T/TR rs121918070 G
Tyrosinemia Type I FAH rs80338899 A
Tyrosinemia Type I FAH rs80338898 T
Tyrosinemia Type I FAH i5012865 A
Tyrosinemia Type I FAH i5012867 T
Tyrosinemia Type I FAH rs121965075 T

 

10 Comments on “Checking Your Carrier Status for Genetic Diseases

  1. Hi, Can you clarify what is the deleterious allele for this snp?

    rs35724775

    23andme reports A or G.

    Thanks!

  2. Rs33971440 (Beta thalassemia)…ummm….I happen to carry this, but with everything else I am fine.

    • Hi – Thanks for reading the blog. Sometimes carriers (one copy) of the beta-thalassemia mutation tend to have lower hemoglobin levels, so it may be something to mention to your doctor.

    • Hi –
      Good question – and one that I need to address more clearly in the article. Everything that I’ve listed on Genetic Lifehacks is in the FWD or plus orientation, which is what 23andMe and AncestryDNA data will match up to. If you have genetic data from another source, you would need to check and see if it lines up with the orientation from dbSNP or if it is always given on the forward strand.

      For rs17580, the two allele choices are A and T, which makes it very confusing when switching between the FWD and REV orientations. For the FWD orientation (23andMe) the risk allele is A.

      For rs28929474, the dbSNP entry you linked to is confusing since it lists all the possible alleles. ClinVar is the database for pathogenic alleles, and it lists the A allele in the REV orientation as the risk allele. (https://www.ncbi.nlm.nih.gov/clinvar/variation/17967/) This would correspond to the T allele in 23andMe (FWD orientation).

      Note that though both of these are listed as pathogenic, they aren’t all that rare. The rs17580 variant is found in more than 3% of the population.

      Hope this helps!
      Debbie

      • Thank you for the follow up. I recently did my DNA test and just started to understand everything. Your web site has been a ton of help.

  3. These showed up on my Promethease work-up… rs12340895(C;G) Increased odds (2 fold?) of developing V617F-positive MPN….. rs3780374(A;G) Substantially increased odds of developing V617F-positive MPN….rs4495487(C;T) Increased odds (2 fold?) of developing V617F-associated MPN. My question is, this does not test exactly for the JAK2 v617f mutation right? It just states that I am at a higher risk of getting that mutation at some point and possible polycythemia vera? Or does it mean that I likely have the mutation?

    • Hi Brandon –
      Having one copy of any of those variants you listed is pretty common — about 40% of people carry the variant.

      The JAK2 V617F mutation is a somatic mutation, which means it is not inherited from your parents. I don’t think 23andMe tests for the JAK2 v617F mutation.

      So those variants that you listed above from Promethease basically double the risk of a JAK2 V617F mutation happening, which is linked to MPN and polycythemia vera. But those are really rare conditions, with a prevalence of 22 per 100,000 people. So even if you double your risk of getting it, it is still unlikely.

      Hope this helps! The information from Promethease can be pretty overwhelming when trying to sort out what is important and what isn’t.
      Debbie

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