Loss of heterozygosity in human colon cancers Figure 7.14 The Biology of Cancer (© Garland Science 2007)

The AS/PWS region of chromosome 15q Redrawn and updated from Jiang et al. Am J Hum Genet 65:1-6 (1999)

22q11 deletion di George Syndrome / Velocardiofacial Syndrome Findings can include Dysmorphic appearance/short stature Cleft palate Conotruncal heart defects Developmental delay Immunologic abnormalities Hypocalcemia Psychiatric illness Sporadic or autosomal dominant There are many associated abnormalities which may sometimes be transmitted as a dominantly inherited condition

Chromosomal structural variants with phenotypic effects from Sharp et al. Annu Rev Genomics Hum Genet 7:407-442, 2006

individual value mean & 95% c.i. Sachse et al. Am J Hum Genet 60:284-295 (1997)

Examples of diseases associated with triplet repeat expansion repeat repeat Type Disease MIM mode sequence location normal pre-mut’n mutation I HD 143100 AD CAG ORF 6 - 34 -- 36 - 121 I SCA1 164400 AD CAG ORF 6 - 39 -- 41 - 81 I SCA2 183090 AD CAG ORF 15 - 29 -- 35 - 59 I MJD 109150 AD CAG ORF 13 - 36 -- 68 - 79 II DM 160900 AD CTG 3' UTR 5 - 37 ~50 - 180 ~200 - >2000 II FRAXA 309550 X* CGG 5' UTR 6 - 35 55 - 200 200 - >2000

Size of SCA7 repeat correlates with age of disease onset redrawn from Giunti et al. Am J Hum Genet 64:1594(1999)

from Zoghbi HY, “The expanding world of ataxins” (Nature Genetics 14:237-238, 1996)

Inheritance of fragile-X alleles and phenotypes PARENT XfX+ XfX+ XfY carrier female affected female transmitting male CHILDREN 25% X+X+ 25% X+X+ -- normal female normal female 25% X+Y 25% X+Y 50% X+Y normal male normal male normal male ----------------------------------------------------------------------------- 8% XfX+ 14% XfX+ -- affected female affected female 17% XfX+ 11% XfX+ 50% XfX+ carrier female carrier female carrier female 19% XfY 25% XfY -- affected male affected male 6% XfY -- -- transmitting male