Genetics


Every person starts out life as a single tiny cell. The information that tells the cell how to build a human body is stored in an encyclopedia of information known as the DNA. This encyclopedia is divided into thousands of short chapters, called genes. Each gene contains the information for building one tiny part of the body, like a piece of liver or muscle.

One tiny cell cannot direct the whole operation of building the whole human body. To accomplish this huge task, it copies its entire encyclopedia of DNA for each new cell it produces. Each new cell then focuses on one part of the encyclopedia and uses the information to assist in the building process. Sometimes the machines that copy the genes for new cells make mistakes. Other times, the genes are damaged for unknown reasons. When this happens, the new cells no longer have the right information in the DNA encylopedia to build the body correctly.

Lesch-Nyhan disease is one of many genetic diseases that occur because of an error in a single gene. In the case of Lesch-Nyhan disease, the gene is called hprt. Extensive research efforts have already uncovered many of the genetic errors, known as mutations, responsible for disease. A list of the known mutations can be found in the Research section.

Silent carrier

All males have one X-chromosome, and all females have two X-chromosomes. Males get Lesch-Nyhan disease when there is a mutation of the hprt gene on the X-chromosome. Females do not get the disease because the normal X-chromosome protects them. These females are known as silent carriers, because they carry the disease, but it remains silent.

Females who are carriers can pass the good chromosome or the bad chromosome to their children. If they pass the good one along, their children are healthy. If they pass the bad one along, the result depends on whether they have a boy or a girl. If the bad chromosome is passed along to a daughter, the daughter is normal but becomes a silent carrier like her mother. If the bad chromosome is passed to a son, he gets Lesch-Nyhan disease. Because every boy inherits his X-chromosome from his mother, only mothers can transmit the disease. Fathers cannot pass the disease to their sons.

Lesch-Nyhan boys do not always get their condition from their mothers. In some cases, their mothers do not carry a bad gene, and they are normal. These boys got their disease when a mutation in the hprt gene occurred very early during their development. Genetic testing is required to determine if the mutation came from the mother or not.

HPRT gene

The hprt gene is located on the long arm of the X chromosome, it's exact position is at Xq26.1.

The information in a gene is coded as a chain of four letters (A, G, C, and T), which are abbreviations for four corresponding molecules (adenine, guanine, cytosine and thymine) residues, in a specific order. Body cells use this information to assemble proteins from amino acids. Proteins form the machinery of a cell, and each protein serves a specific function. See here for more information on what the protein HPRT does.

The following table shows the genetic code for the hprt gene and the amino acid sequence for the protein. Using the genetic code, it is possible to predict the amino acid changes for specific mutations. A detailed list of known mutations is available in the Research section.

ExonPositionBaseCodonAminoacid
11A
12T1met
13G
14G
15C2ala
16G
17A
18C3thr
19C
110C
111G4arg
112C
113A
114G5ser
115C
116C
117C6pro
118T
119G
120G7gly
121C
122G
123T8val
124C
125G
126T9val
127G
228A
229T10ile
230T
231A
232G11ser
233T
234G
235A12asp
236T
237G
238A13asp
239T
240G
241A14glu
242A
243C
244C15pro
245A
246G
247G16gly
248T
249T
250A17tyr
251T
252G
253A18asp
254C
255C
256T19leu
257T
258G
259A20asp
260T
261T
262T21leu
263A
264T
265T22phe
266T
267T
268G23cys
269C
270A
271T24ile
272A
273C
274C25pro
275T
276A
277A26asn
278T
279C
280A27his
281T
282T
283A28tyr
284T
285G
286C29ala
287T
288G
289A30glu
290G
291G
292A31asp
293T
294T
295T32leu
296G
297G
298A33glu
299A
2100A
2101G34arg
2102G
2103G
2104T35val
2105G
2106T
2107T36phe
2108T
2109A
2110T37ile
2111T
2112C
2113C38pro
2114T
2115C
2116A39his
2117T
2118G
2119G40gly
2120A
2121C
2122T41leu
2123A
2124A
2125T42ile
2126T
2127A
2128T43met
2129G
2130G
2131A44asp
2132C
2133A
2134G45arg
2135G
3136A
3137C46thr
3138T
3139G
3140A47glu
3141A
3142C
3143G48arg
3144T
3145C
3146T49leu
3147T
3148G
3149C50ala
3150T
3151C
3152G51arg
3153A
3154G
3155A52asp
3156T
3157G
3158T53val
3159G
3160A
3161T54met
3162G
3163A
3164A55lys
3165G
3166G
3167A56glu
3168G
3169A
3170T57met
3171G
3172G
3173G58gly
3174A
3175G
3176G59gly
3177C
3178C
3179A60his
3180T
3181C
3182A61his
3183C
3184A
3185T62ile
3186T
3187G
3188T63val
3189A
3190G
3191C64ala
3192C
3193C
3194T65leu
3195C
3196T
3197G66cys
3198T
3199G
3200T67val
3201G
3202C
3203T68leu
3204C
3205A
3206A69lys
3207G
3208G
3209G70gly
3210G
3211G
3212G71gly
3213C
3214T
3215A72tyr
3216T
3217A
3218A73lys
3219A
3220T
3221T74phe
3222C
3223T
3224T75phe
3225T
3226G
3227C76ala
3228T
3229G
3230A77asp
3231C
3232C
3233T78leu
3234G
3235C
3236T79leu
3237G
3238G
3239A80asp
3240T
3241T
3242A81tyr
3243C
3244A
3245T82ile
3246C
3247A
3248A83lys
3249A
3250G
3251C84ala
3252A
3253C
3254T85leu
3255G
3256A
3257A86asn
3258T
3259A
3260G87arg
3261A
3262A
3263A88asn
3264T
3265A
3266G89ser
3267T
3268G
3269A90asp
3270T
3271A
3272G91arg
3273A
3274T
3275C92ser
3276C
3277A
3278T93ile
3279T
3280C
3281C94pro
3282T
3283A
3284T95met
3285G
3286A
3287C96thr
3288T
3289G
3290T97val
3291A
3292G
3293A98asp
3294T
3295T
3296T99phe
3297T
3298A
3299T100ile
3300C
3301A
3302G101arg
3303A
3304C
3305T102leu
3306G
3307A
3308A103lys
3309G
3310A
3311G104ser
3312C
3313T
3314A105tyr
3315T
3316T
3317G106cys
3318T
4319A
4320A107asn
4321T
4322G
4323A108asp
4324C
4325C
4326A109gln
4327G
4328T
4329C110ser
4330A
4331A
4332C111thr
4333A
4334G
4335G112gly
4336G
4337G
4338A113asp
4339C
4340A
4341T114ile
4342A
4343A
4344A115lys
4345A
4346G
4347T116val
4348A
4349A
4350T117ile
4351T
4352G
4353G118gly
4354T
4355G
4356G119gly
4357A
4358G
4359A120asp
4360T
4361G
4362A121asp
4363T
4364C
4365T122leu
4366C
4367T
4368C123ser
4369A
4370A
4371C124thr
4372T
4373T
4374T125leu
4375A
4376A
4377C126thr
4378T
4379G
4380G127gly
4381A
4382A
4383A128lys
4384G
5385A
5386A129asn
5387T
5388G
5389T130val
5390C
5391T
5392T131leu
5393G
5394A
5395T132ile
5396T
5397G
5398T133val
5399G
5400G
5401A134glu
5402A
6403G
6404A135asp
6405T
6406A
6407T136ile
6408A
6409A
6410T137ile
6411T
6412G
6413A138asp
6414C
6415A
6416C139thr
6417T
6418G
6419G140gly
6420C
6421A
6422A141lys
6423A
6424A
6425C142thr
6426A
6427A
6428T143met
6429G
6430C
6431A144gln
6432G
6433A
6434C145thr
6435T
6436T
6437T146leu
6438G
6439C
6440T147leu
6441T
6442T
6443C148ser
6444C
6445T
6446T149leu
6447G
6448G
6449T150val
6450C
6451A
6452G151arg
6453G
6454C
6455A152gln
6456G
6457T
6458A153tyr
6459T
6460A
6461A154asn
6462T
6463C
6464C155pro
6465A
6466A
6467A156lys
6468G
6469A
6470T157met
6471G
6472G
6473T158val
6474C
6475A
6476A159lys
6477G
6478G
6479T160val
6480C
6481G
6482C161ala
6483A
6484A
6485G162ser
7486C
7487T
7488T163leu
7489G
7490C
7491T164leu
7492G
7493G
7494T165val
7495G
7496A
7497A166lys
7498A
7499A
7500G167arg
7501G
7502A
7503C168thr
7504C
7505C
7506C169pro
7507A
7508C
7509G170arg
7510A
7511A
7512G171ser
7513T
7514G
7515T172val
7516T
7517G
7518G173gly
7519A
7520T
7521A174tyr
7522T
7523A
7524A175lys
7525G
7526C
7527C176pro
7528A
7529G
7530A177asp
7531C
8532T
8533T178phe
8534T
8535G
8536T179val
8537T
8538G
8539G180gly
8540A
8541T
8542T181phe
8543T
8544G
8545A182glu
8546A
8547A
8548T183ile
8549T
8550C
8551C184pro
8552A
8553G
8554A185asp
8555C
8556A
8557A186lys
8558G
8559T
8560T187phe
8561T
8562G
8563T188val
8564T
8565G
8566T189val
8567A
8568G
8569G190gly
8570A
8571T
8572A191tyr
8573T
8574G
8575C192ala
8576C
8577C
8578T193leu
8579T
8580G
8581A194asp
8582C
8583T
8584A195tyr
8585T
8586A
8587A196asn
8588T
8589G
8590A197glu
8591A
8592T
8593A198tyr
8594C
8595T
8596T199phe
8597C
8598A
8599G200arg
8600G
8601G
8602A201asp
8603T
8604T
8605T202leu
8606G
8607A
8608A203asn
8609T
9610C
9611A204his
9612T
9613G
9614T205val
9615T
9616T
9617G206cys
9618T
9619G
9620T207val
9621C
9622A
9623T208ile
9624T
9625A
9626G209ser
9627T
9628G
9629A210glu
9630A
9631A
9632C211thr
9633T
9634G
9635G212gly
9636A
9637A
9638A213lys
9639A
9640G
9641C214ala
9642A
9643A
9644A215lys
9645A
9646T
9647A216tyr
9648C
9649A
9650A217lys
9651A
9652G
9653C218ala
9654C
9655T
9656A219stop
9657A