Chapter 7 Mendel’s Laws Predict the inherited traits Exceptions to Mendel’s Laws X inactivation turns off entire chromosomes but genomic imprinting turns off specific genes Now we will look at … Disease causing genes (both autosomal and sex linked disorders) Entire chromosomes but genomic imprinting turns off specific genes

Are sex chromosomes present in your skin cells? Yes No Ans:A

22 pairs of non-sex chromosomes and 1 pair of sex chromosomes

Human Genetic Disorders (> 1000; controlled by a single gene) X- linked Disorders Autosomal Disorders dominant recessive recessive Dominant

Autosomal Recessive disorders -more common -homozygous recessive to show symptoms -heterozygous…..carriers -Example: Cystic fibrosis, sickle-cell, Tay-Sachs disease, Fanconi anemia

Cystic Fibrosis Autosomal recessive (CF gene on chromosome 7) http://www.ygyh.org/cf/inherited.htm (cystic fibrosis animation)

If the father is a carrier for cystic fibrosis and the mother is normal, what are the chances that their child will have the disease ? 100% 50% 25% 0% Ans: D

Autosomal Dominant disorder -Much less common -Some are nonlethal while others are lethal -Examples: Achondroplasia Huntington’s disease Fatal familial insomnia Osteogenesis imperfecta Williams syndrom: learning disability; elfin features, music talent

Cause: Autosomal dominant gene Huntington’s Disease Cause: Autosomal dominant gene A person with Huntington’s disease has a ______ chance of passing the disorder on to their offspring. H h h Hh hh Hh hh h Problem: Symptoms usually don’t show until ___ So you don’t know you have it until after you have had children

Can you carry the allele for an autosomal dominant disorder and not show the symptoms? Yes, b’cos 2 copies are needed to show symptoms B. No, b’cos only 1 copy is needed to show symptoms Ans: B

Human Genetic Disorders (> 1000; controlled by a single gene) X- linked Disorders Autosomal Disorders dominant recessive Dominant recessive

X linked recessive traits – more men have this disorder than women. Hemophilia Color blindness Muscular Dystrophy X linked traits can be dominant! more women have this disorder than men! Very rare: Vit D resistant ricketts Rett syndrome Ricketss (soft bones) cannot be treated or is resistant to vit D treatment Rett syndrome the brain does not develop well

Hemophilia is a recessive sex linked trait. What is the genotype of … A normal woman whose father had hemophilia A normal man whose father had hemophilia

-affected male is lethal X linked dominant Rett syndrome -affected male is lethal

Fetal testing Detect inherited disorders in pregnancy using: Amniocentesis Chorionic villus sampling Ultrasound imaging

A woman who is a carrier for the recessive, sex-linked trait red color blindness, marries a normal male. What is the chance that their daughters will be color blind? All 50 % 25% 75% Ans: 0

Using pedigrees to decipher and predict the inheritance patterns of genes. Pedigree a type of family tree People want to know things about the future, such as: what is the likelihood that I will have a child with a particular genetic disease, say hemophilia? Or, what is my own risk of developing a genetic disease such as Huntington’s disease later in my life? Geneticists who study these and other diseases want to know how they are passed along. Are they recessive or dominant? Are they carried on the sex chromosomes or one of the other chromosomes? A pedigree is a type of family tree that can help to answer these questions. In a pedigree, information is gathered from as many related individuals as possible across multiple generations. Starting from the bottom, each row in the chart represents a generation, listing all of the children in their order of birth and whether or not they express a particular trait. Working up the pedigree, their parents are indicated and above them, their parents, for as far back as the data are available. Squares represent males and circles represent females, and these shapes are shaded to indicate that an individual exhibits the trait of interest. Sometimes the genotype (as much of it as is known) is also listed for each individual.   By analyzing which individuals manifest the trait and which do not, it may be possible to deduce the pattern of inheritance for the trait—or, at least, rule out certain patterns. For example, if an individual exhibits a trait that neither of their parents exhibits, the trait is recessive. For dominant traits, all affected individuals must have at least one parent who exhibits the trait. In contrast, an individual can exhibit a recessive trait even if both parents are unaffected. In this case, the individual’s parents would have to be heterozygous for that trait, each carrying one dominant gene and one recessive gene. Similarly, it is sometimes possible to determine whether a trait is carried on the sex chromosomes or one of the non-sex chromosomes (i.e., the autosomes). Traits that are controlled by genes on the sex chromosomes are called sex-linked traits. Recessive sex-linked traits, for example, appear more frequently in males than females while dominant sex-linked traits appear more frequently in females. These patterns may become obvious only upon inspection of a large pedigree. 17

Sex-Linked Traits The pedigree can also help to determine whether a trait is carried on the sex chromosomes or on one of the non-sex chromosomes (i.e., the autosomes). Traits that are controlled by genes on the sex chromosomes are called sex-linked traits. Recessive sex-linked traits, for example, appear more frequently in males than females, whereas dominant sex-linked traits appear more frequently in females. These patterns may become obvious only upon inspection of a large pedigree. An example of how pedigrees can help determine how traits are inherited is given in the pedigree in Figure 7-17. Anury is a condition seen in dogs and some other animals in which they have no tail. The pedigree reveals that anury is inherited as a recessive trait because unaffected parents can have offspring with the disorder.   Can you figure out the genotype of the individual labeled “1”? That individual must be heterozygous (Aa) for anury and a carrier of the recessive gene because she doesn’t show the trait but has offspring that do. On the same pedigree, note that the first and second individuals from the left in the second generation have a puppy (indicated by the ‘?’). What is the probability that this puppy has anury? In that cross the father must be homozygous recessive because he has anury; he will definitely pass on one “a” to the son. The mother’s genotype can be AA, Aa, or aA, given that her parents are both heterozygous. Consequently, she has a 2/3 probability of carrying the “a” allele. If she does, then there is a one in two (50%) chance that she will pass it on to her offspring and he will have anury. The probability, therefore, is 2/3 * ½ = 1/3 that the puppy will have anury. 18

Xn = colorblindness allele XN = normal allele Xn = colorblindness allele Fully shaded: has the trait Partially shaded: is a carrier (not all pedigrees will have the partial shading) Not shaded: does not have the trait

Is George colorblind? Yes No Ans:B

Autosomal dominant Autosomal dominant…see it in every generation and both males and females affected and B. is mutation

Autosomal Recessive Typical pedigree of an autosomal-recessive disorder. Note horizontal transmission and presence of consanguinity. In AR disorders (Fig. 4), both males and females are affected, and the pedigree shows a horizontal pattern of inheritance (i.e. affected siblings).

Sex-Linked Recessive More males affected

Individual Activity (5 pts) The following pedigree follows a sex linked recessive trait. Circle all of the persons you are certain are carriers. Carriers are people who carry the allele but show/express no symptoms. Hint: Only 4 people