GENETICS 101 This documet is iteded to provide a basic uderstadig of caie geetics to the America Eskimo Dog (AED) ower ad breeder. It is simplified from scietific facts ad uderstadig. It is ot iteded to be a complete discussio of the material, ad readers are urged to study o their ow through ay excellet sources o the Iteret, especially the AKC Caie Health Foudatio (CHF) which has podcasts of timely health topics. Other liks may be foud below. This page will be modified ad expaded as time permits ad ew topics arise. AEDCA members are urged to cotact members of the AEDCA Health Committee with subjects about which they are cocered. GLOSSARY Allele meas oe copy of a pair of gees located at the same locatio (locus) i paired chromosomes. For each gee, oe allele is iherited from the sire ad oe from the dam. Autosomal meas the all of the gees ot foud o a sex chromosome (the X ad Y chromosomes). Complex iheritace meas that several gees are ivolved i the expressio of a trait. A syoymous term is polygeetic iheritace. Domiace meas a relatioship betwee the alleles of a gee i which oe allele masks the expressio (pheotype) of aother allele at the same locus. Gee meas a hereditary uit, ordiarily at a fixed positio o a chromosome that iflueces a particular trait ad made up of two alleles. Geotype meas the geetic make-up of a idividual, either at a sigle locus or overall of its gees collectively. Heterozygous meas that the two alleles of a sigle gee are differet. Oe allele will be domiat (the oe that the idividual expresses) ad oe will be recessive (ot expressed but ca be passed o to offsprig). Homozygous meas that the two alleles of a sigle gee are the same ad is the oly allele that the idividual ca pass o to its offsprig. Pheotype meas the physical characteristic which is expressed i the idividual. Recessive meas that the allele withi a gee is ot expressed but may be passed o to offsprig. Simple iheritace meas that oly oe gee is resposible for the expressio of a trait. Other terms pertaiig to other modes of iheritace ad various biochemical reactios ad markers are more advaced tha this summary will discuss. Readers are urged to go o-lie ad read more about the facet of geetics that may iterest them. Uderstadig geetics ca be cofusig because may breeders commoly use the terms gee ad allele iterchageably; however, these words have differet ad precise meaigs. Aother cofusig aspect of geetics is that mutatios ca occur spotaeously, ad o oe ca predict their occurrece- this is the reaso that breeders must be costatly vigilat.
Simple Autosomal Recessive Geetics Let s quickly review what this term meas by lookig back at our glossary. Simple meas that we are talkig about a trait, which ca iclude a disease, caused oe gee. Autosomal meas that we are talkig about gees foud o ay chromosome except the sex chromosomes, X ad Y. Each idividual has two alleles for each gee. If the alleles are the same, the idividual is homozygous for that trait ad it will be expressed. If the alleles are differet, the idividual is said to be heterozygous; ad the domiat allele will be expressed, ad the recessive allele will be hidde. Most breeders thik of simple autosomal recessive traits whe they thik about caie geetics. To illustrate how this mode of iheritace works, let s use the example of progressive rod-coe dysplasia (prcd) form of Progressive Retial Atrophy (PRA) i America Eskimo Dogs. We ca write the domiat allele for Normal as a capital N; ad the recessive allele (the mutatio) as small-case. A homozygous Normal Eskie will be writte as NN ad a Affected homozygous Eskie as. By defiitio of a recessive trait, a Affected Eskie is homozygous ad has two copies of the mutatio; ad the term homozygous Affected is actually a redudat statemet. However, a heterozygous Carrier Eskie will have oe of each of the two alleles ad be writte as N. I simple autosomal recessive diseases like prcd-pra, Normal is domiat to Affected. The heterozygous Carrier Eskie will ever develop prcd-pra but ca pass alog the mutat allele to its offsprig. Differetiatig betwee the pheotypically-idetical Normal ad Carrier Eskies (both will ever develop the disease) was the historical problem that breeders had i the past. Breeders had o way of lookig at the geotype of the Normal ad Carrier to see the differece- this is what moder geetic testig allows us to do. I the old days, wheever a Affected Eskie was produced, breeders kew that both parets were Carriers. However, with a late-oset disease such as prcd-pra i the Eskie, the offsprig were likely six years of age or older before they developed the disease ad breeders kew the parets status; ad those parets were ofte dead or at least retired from breedig. That left the problem of determiig the geetic status of the Affected Eskie s offsprig ad what mates would be appropriate for them. May breeders solved that questio be decidig to termiate breedig ay of the descedats of the Affected Eskies, thus removig their diversity from the breed s gee pool. Moder geetic testig allows breeders to retai Carriers ad Affecteds i a resposible breedig program. Let us cosider the six possible matig combiatios for a simple autosomal recessive disease such as prcd-pra i America Eskimo Dogs: 1. Homozygous Normal to homozygous Normal- This matig ca be writte as NN x NN ad all offsprig will all be homozygous Normal (NN). Optige refers to this matig as Patter A x Patter A. 2. Homozygous Affected to homozygous Affected- This matig ca be writte x ad all offsprig will all be homozygous Affected (). OptiGe refers to this matig as Patter C x Patter C. 3. Homozygous Normal to homozygous Affected- This matig ca be writte as NN x ad all offsprig will be heterozygous Carrier (N). Optige refers to this matig as Patter A x Patter C. We ca draw a table showig oe paret s alleles dow the shaded left side (NN) ad the other paret s alleles alog the shaded top (). Each paret cotributes oe allele to each offsprig, so the resultig gee combiatios ca be writte i the remaider of the table.
N N N N N N 4. Homozygous Normal to a heterozygous Carrier- This matig ca be writte as NN x N. Half (50%) of the offsprig will be homozygous Normal (NN) ad 50% will be heterozygous Carrier (N). OptiGe refers to this matig as Patter A x Patter B. N N NN N N NN N 5. Homozygous Affected to a heterozygous Carrier- This matig ca be writte as x N. Half (50%) of the offsprig will be heterozygous Carrier (N) ad 50% will be homozygous Affected (). OpitGe refers to this matig as Patter C x Patter B. N 6. Heterozygous Carrier to a heterozygous Carrier- This matig ca be writte as N x N ad results i the greatest diversity of offsprig- 25% will be homozygous Normal (NN), 50% will be heterozygous Carrier (N), ad 25% will be homozygous Affected (). OpitGe refers to this matig as Patter B x Patter B. N N NN N The odds provided for the prcd-pra Eskies i the scearios from the matigs show i 3 through 6 above are for large populatios; however, ay litter could be all of ay oe of the possibilities for that matig. The odds of producig Normal, Carrier, ad/or Affected Eskies from the scearios show i 3 through 6 are idepedet variables. This meas that each puppy i the litter is uique, ad each puppy has a equal chace of beig oe of the possible combiatios without ay ifluece from the other puppies i the litter. It is the same as the odds for the sex of a puppy- it ca be either male or female, ad each puppy has a 50% chace of beig male or female. The sex of oe puppy has othig to do with the sex of aother puppy i the same litter. Overall i a large populatio of puppies, we see approximately the same umber of males as females; but withi oe litter we could have all of oe sex or the other. The goal of ay breedig program is to ever produce Affected aimals. For autosomal recessive diseases, if we ca idetify the heterozygous Carriers (Patter B or N) ad homozygous Affecteds (Patter C or ) ad ever breed them to ay Eskie except a homozygous Normal (Patter A or NN), the we ca still use Carrier ad Affected Eskies i a resposible breedig program. Maitaiig geetic diversity i the breed while producig Eskies of strog metal ad physical health should be our goal. Whe breeders select oly homozygous Normal (Patter A or NN) Eskies, they are effectively removig all Affecteds ad Carriers from the gee pool today. Our goal should be to keep as may Eskies as possible i our breedig programs for the geetic diversity they provide, so that we icrease the umbers of idividuals to maitai geetic diversity.
Breeders should pla to replace each Affected or Carrier Eskie with a Normal offsprig sometime durig the life of the Affected or Carrier. The time period could be i two years or te years because each breeder ad situatio is uique. AED breeders should ot be i a rush to remove all Carriers ad Affecteds as they have a ecessary place i a maaged breedig program. Aother iterestig ote is that OptiGe states o their website that ay America Eskimo Dog which tests as a Affected ( or Patter C) will develop the disease. The prcd form of PRA i the Eskie is late-oset ad may ot start to affect the Eskie util 10 or 12 years of age; or it may ot result i total blidess before the AED dies. If you have or kow of Eskies which test as Patter C, or Affected, ad are at least 10 years old ad have ot developed prcd-pra, you should arrage for your Eskies to be examied by OptiGe or oe of their ophthalmologists. If you caot get your dogs to them, you should at least make cotact them to let them kow of your situatio. Breeders ad owers have several optios to assist research scietists, icludig doatig tissue to the scietists upo a Eskie s death. While this is a difficult emotioal decisio, owers should cosider this possibility before your Eskie passes ad make arragemets with your vet before your beloved Eskie passes. This doatio is truly a gift to the breed s future. Simple Autosomal Domiat Geetics Domiat diseases should cocer all breeders because they pose a eve greater threat tha recessive diseases. Let s quickly review our glossary. Simple meas that we are talkig about a trait, which ca iclude disease, caused oe gee. Autosomal meas that we are talkig about gees foud o ay chromosome except the sex chromosomes, X ad Y. Each idividual has two alleles for each gee. If the alleles are the same, the idividual is homozygous for that trait ad it will be expressed. If the alleles are differet, the idividual is said to be heterozygous; ad the domiat allele will be expressed, ad the recessive allele will be hidde. Most Eskie breeders thik of simple autosomal recessive traits whe they thik about caie geetics. Our breed is ot believed to have ot bee affected by a simple domiat disease, but all it would take is a sigle mutatio i the right place. If the disease is late-oset like prcd-pra, we would t eve kow of the problem for several years; ad by the we could have real problems o our hads. Why the gloom ad doom? Let s look at how a simple domiat disease could hurt our breed. Three possibilities exist for the geotype of ay idividual i a simple trait- two are homozygous ad oe is heterozygous. Geeticists prefer to write a domiat trait as capital letters ad recessive traits as small letters. We ca write homozygous Affected as AA ad homozygous Normal as. The heterozygous Eskie is writte as A ad will develop the disease because i the domiat disease oly oe copy of the mutat allele eeds to be preset. We would o loger refer to heterozygous Eskies as heterozygous Carriers but as heterozygous Affecteds. Out of the three possible geotypes, two will have disease- far differet tha the oe-i-three possibilities of the recessive disease. Let s look at some possible matigs ad their outcomes whe dealig with simple domiat traits: 1. Homozygous Affected (AA) mated to a homozygous Normal ()- All offsprig are heterozygous Affected (A) ad will have the disease.
A A A A A A Obviously a homozygous Affected Eskie (AA) would be devastatig to the breed because eve whe bred to a geetic Normal (), all of its offsprig will be heterozygous Affected ad will have the disease. 2. Heterozygous Affected (A) mated to a homozygous Normal ()- Half of the offsprig (50%) will be heterozygous Affected (A) ad will have the disease; ad 50% will be homozygous Normal (). A A A The would be the best-case breedig sceario usig a heterozygous Affected Eskie (A) ad would result i 50% heterozygous Affected Eskies which will develop the disease. 3. Heterozygous Affected (A) mated to a heterozygous Affected (A)- Matigs of heterozygous aimals produce the greatest variatio i offsprig. Oe-fourth (25%) of the offsprig will be homozygous Affected (AA); half (50%) will be heterozygous Affected (A); ad oe-fourth (25%) will be homozygous Normal (). The ed result is that 75% of the offsprig (25% as AA plus 50% as A) will have the disease. A A AA A A Obviously, a autosomal domiat disease would be much more devastatig tha a simple autosomal recessive disease such as prcd-pra i the America Eskimo Dog. Other breeds of dogs ad aimals have geetic disease issues which are caused by simple domiat gees, ad the solutios are ot so simple.