Genetics and inheritance Questions with true or false answers

1. Genetics and inheritanceQuestions with true or false answers • Here are a selection of questions on genetics and inheritance, all with true or false answers. Just delete any questions that you do not want to use. • Chromosomes and genes • Alleles are alternative forms of a gene at the same locus. • Human chromosome analysis by light microscopy can be performed only on peripheral blood cells. • There are 45 autosomes in the normal human karyotype. • Clinical aspects • When drawing a pedigree, a filled in circle is used to denote a female with a medical condition. • Prenatal diagnosis by DNA analysis can only be performed on tissue in which the gene is being expressed. • The primary purpose of genetic counselling is to reduce the incidence of genetic disease in the population. • Genetic testing in childhood should be performed only for conditions where genetic information will enable surveillance for complications. • More than 40% of children who have congenital sensory neural deafness have a genetic cause.

2. Genetics and inheritanceQuestions with true or false answers • Autosomal dominant • The son of a woman with an autosomal dominant condition has a 1 in 2 chance of inheriting the condition. • A daughter of a woman with an autosomal dominant condition has a 1 in 2 chance of inheriting the condition. • Not all children with an autosomal dominant condition (such as neurofibromatosis) will have a parent with the condition. • A particular characteristic of autosomal dominant inheritance is that all people with the condition in a family will demonstrate exactly the same degree of severity. • Autosomal recessive • Males and females are affected in equal proportions in autosomal recessive inheritance. • A carrier is a healthy person who is a heterozygote for a recessive condition. • The healthy sib of a person with an autosomal recessive condition has a probability of 1 in 2 of being a carrier. • The healthy brothers and sisters of a child with congenital adrenal hyperplasia have a 2 out of 3 chance of being a carrier. • If the first child of two parents who are carriers has sickle cell disease the next three children will not inherit the condition. • Artificial insemination with donor sperm will greatly reduce the chance of a couple with a baby with a rare autosomal recessive condition, having another baby with the condition. • Approximately 1 in 20 of the white population in the UK is a carrier for cystic fibrosis. • It can be difficult to detect carriers of autosomal recessive metabolic diseases (such as congenital adrenal hyperplasia) by biochemical assay because of the overlap of levels with the normal range.

3. Genetics and inheritanceQuestions with true or false answers • X-linked • Females are never affected with X-linked recessive diseases. • A male with an X-linked condition does not pass on the condition to his sons. • Each son of a man with haemophilia A has a 1 in 2 chance of inheriting the condition. • The mothers of all boys with Duchenne muscular dystrophy are carriers for the condition. • The sister of two boys who have X-linked adrenoleukodystrophy has a 1 in 2 chance of being a carrier. • Chromosomes • The majority of people with Down syndrome have trisomy 21. • Different physical characteristics on examination would allow one to predict whether a baby boy had the karyotype 47, XY+21 (trisomy 21) or an unbalanced 14-21 Robertsonian translocation. • Robertsonian translocations are found in 25% of people with Down syndrome. • Reciprocal translocations are rarely inherited. • Children who are carriers of balanced reciprocal translocations can usually be diagnosed because of their dysmorphic features. • The karyotype XYY is associated with gynaecomastia, tall stature, infertility and eunuchoid habitus.

4. Genetics and inheritanceQuestions with true or false answers • Multifactorial • The chance of having another child with a neural tube defect is 1 in 200. • The environmental component of the majority of multifactorial conditions has been identified. • Mitochondrial • The children of a man with a condition caused by a mutation in mitochondrial DNA will not inherit the condition from him.

5. Genetics and inheritanceQuestions with true or false answers • Here are a selection of questions on genetics and inheritance, together with the true or false answers. • Chromosomes and genes • 1. Alleles are alternative forms of a gene at the same locus. • True • 2. Human chromosome analysis by light microscopy can be performed only on peripheral blood cells. • False • Chromosome analysis can be performed on almost any dividing cells - commonly on skin fibroblasts, amniocytes and chorionic villus cells. • 3. There are 45 autosomes in the normal human karyotype. • False • There are 44 (22 pairs) autosomes in the normal human karyotype. An autosome is any chromosome other than the sex (X or Y) chromosome. • Clinical aspects • 1. When drawing a pedigree, a filled in circle is used to denote a female with a medical condition. • True • Females are designated by circles, males by squares. A diamond is used if the sex is unknown. A coloured in symbol denotes a person who has a medical condition. • 2. Prenatal diagnosis by DNA analysis can only be performed on tissue in which the gene is being expressed. • False • All somatic cells have the same nuclear DNA code with copies of all the genes (apart from reticulocytes which lose their nuclei), although not all genes are expressed in all tissues. The advantage of DNA analysis is that the gene which is not being actively expressed in a particular cell type can still be analysed by looking directly at the DNA code.

6. Genetics and inheritanceQuestions with true or false answers • Clinical aspects continued • 4. The primary purpose of genetic counselling is to reduce the incidence of genetic disease in the population. • False • Genetic counselling is an information giving process by which patients or relatives at risk of a genetic disorder are given information about the consequences of the disorder, the probability of developing or transmitting it, and the ways in which this may be prevented or ameliorated. It should be “non-directive”, allowing families to make their own choices. • 5. Genetic testing in childhood should be performed only for conditions where genetic information will enable surveillance for complications. • True • There is international agreement that children should not be tested for carrier status or adult onset conditions until they are at an age where they can make an informed decision. • 6. More than 40% of children who have congenital sensory neural deafness have a genetic cause. • True • Single gene disorders are the cause of about 50% of congenital sensory neural deafness (the majority being autosomal recessive). Environmental and idiopathic factors make up 30% and 20%. • Autosomal dominant • 1. The son of a woman with an autosomal dominant condition has a 1 in 2 chance of inheriting the condition. • True • 2. A daughter of a woman with an autosomal dominant condition has a 1 in 2 chance of inheriting the condition. • True • Each child (regardless of sex) has a 1 in 2 chance of inheriting the altered gene.

7. Genetics and inheritanceQuestions with true or false answers • Autosomal dominant continued • 3. Not all children with an autosomal dominant condition (such as neurofibromatosis) will have a parent with the condition. • True • Some people have an autosomal dominant condition as the result of a new mutation occurring in the sperm or egg which went to make that person. Of course, such a person can then pass the autosomal dominant condition onto his or her children. • 4. A particular characteristic of autosomal dominant inheritance is that all people with the condition in a family will demonstrate exactly the same degree of severity. • False • For most autosomal dominant conditions, there is considerable variability between people both within and between families. This is called ‘variation in expression’ and requires detailed physical examination of people at risk within the family. • Autosomal recessive • 1. Males and females are affected in equal proportions in autosomal recessive inheritance. • True • 2. A carrier is a healthy person who is a heterozygote for a recessive condition. • True • Also refers to a person with a balanced chromosomal translocation. • 3. The healthy sib of a person with an autosomal recessive condition has a probability of 1 in 2 of being a carrier. • False • In autosomal recessive inheritance, there are four possible genetic patterns that a child conceived to parents who are both carriers can inherit. The 2nd and 3rd possibilities is that the child is a carrier, inheriting one altered copy of the gene and one usual one – one from each parent. The 4th possibility is that the child inherits a copy of the altered gene from both parents, and has the condition. The 1st possibility is that the child inherits the usual copy of the gene from both parents. If we know clinically that the child has not inherited the condition, there are only 3 possibilities left, in two of which the child would be a carrier.

8. Genetics and inheritanceQuestions with true or false answers • Autosomal recessive continued • Therefore the chance that the full sib of someone with an autosomal recessive condition is a carrier is 2 in 3 if we know already that they cannot have the condition. • 4. The healthy brothers and sisters of a child with congenital adrenal hyperplasia have a 2 out of 3 chance of being a carrier. • True • When we know that a sib of someone with an autosomal recessive condition is healthy, it means that they cannot be homozygous for the gene associated with the condition. Of the four possibilities in autosomal recessive segregation, one has therefore been excluded with the resulting 2 out of 3 chance that the sib is a carrier. • 5. If the first child of two parents who are carriers has sickle cell disease the next three children will not inherit the condition. • False • Chance has no memory! The chance in each pregnancy is 1 in 4 of having a child with the condition. • 6. Artificial insemination with donor sperm will greatly reduce the chance of a couple with a baby with a rare autosomal recessive condition, having another baby with the condition. • True • The carrier frequency for the disorder must be known. Although sperm from a donor will reduce the probability, it may still be higher than expected if the autosomal recessive condition is common in the population from which the sperm donor is taken (e.g. the probability before carrier testing that a male in some Mediterranean populations is a carrier for thalassaemia is 1 in 6). • 7. Approximately 1 in 20 of the white population in the UK is a carrier for cystic fibrosis. • True • Of these 75% have the Delta F508 mutation.

9. Genetics and inheritanceQuestions with true or false answers • Autosomal recessive continued • 8. It can be difficult to detect carriers of autosomal recessive metabolic diseases (such as congenital adrenal hyperplasia) by biochemical assay because of the overlap of levels with the normal range. • True • For an increasing number of conditions carrier status with a family can be determined once a mutation in the causative gene has been identified in the affected person. • X-linked • 1. Females are never affected with X-linked recessive diseases. • False • Rarely, a woman can be homozygous for an X-linked condition – e.g. colour blindness, when her father has the condition affected and her mother is a carrier. If a woman has signs of an X-linked recessive condition, then chromosome analysis should be performed to determine if she has a structural anomaly of the X chromosome, or has Turner syndrome. • 2. A male with an X-linked condition does not pass on the condition to his sons. • True • A father passes on his Y chromosome to his sons. All the daughters of a male with an X-linked condition will be obligate carriers. • 3. Each son of a man with haemophilia A has a 1 in 2 chance of inheriting the condition. • False • A man with an X-linked condition passes on his Y chromosome to his sons (all of whom will therefore not have the condition) and his X chromosome to his daughters (all of whom will be carriers). • 4. The mothers of all boys with Duchenne muscular dystrophy are carriers for the condition. • False • In a family where there is an isolated boy with Duchenne muscular dystrophy, there is a 1 in 3 chance that his disease is the result of a mutation occurring for the first time in the egg which went to make him. There is a 2 out of 3 chance that his mother is a carrier. Compare this with the 100% chance that his mother would be a carrier if her brother also had Duchenne muscular dystrophy.

10. Genetics and inheritanceQuestions with true or false answers • X-linked continued • 5. The sister of two boys who have X-linked adrenoleukodystrophy has a 1 in 2 chance of being a carrier. • True • As she has two brothers who have an X-linked condition, her mother must be a carrier. Therefore her mother will pass on either the X chromosome with the usual gene or the X chromosome with the altered gene, giving the sister a 1 in 2 chance of being a carrier. • Chromosomes • 1. The majority of people with Down syndrome have trisomy 21. • True • Down syndrome is most commonly caused by trisomy associated with non disjunction at maternal meiosis. 4% of people with Down syndrome have a Robertsonian translocation involving chromosome 21. • 2. Different physical characteristics on examination would allow one to predict whether a baby boy had the karyotype 47, XY+21 (trisomy 21) or an unbalanced 14-21 Robertsonian translocation. • False • The physical features of a person with Down syndrome caused by either trisomy 21 or an unbalanced Robertsonian translocation are the same. It is therefore important to perform karyotyping in a baby with Down syndrome to exclude the possibility of a translocation. • 3. Robertsoniantranslocations are found in 25% of people with Down syndrome. • False • A Robertsonian translocation is the cause of Down syndrome in <5% of people with Down syndrome. When found, parents should be karyotyped to determine if the translocation is inherited, in which case other family members may have a high probability of having the translocation. • 4. Reciprocal translocations are rarely inherited. • False • Reciprocal translocations can occur between any chromosomes, and are usually inherited. One partner in 1 in 20 couples with recurrent miscarriages is said to be a translocation carrier.

11. Genetics and inheritanceQuestions with true or false answers • Chromosomes continued • 5. Children who are carriers of balanced reciprocal translocations can usually be diagnosed because of their dysmorphic features. • False • By definition a carrier of a balanced reciprocal translocation will show no effects - there has been no gain or loss of genetic material. • 6. The karyotype XYY is associated with gynaecomastia, tall stature, infertility and eunuchoidhabitus. • False • The description is of a patient with features of Klinefelter syndrome, XXY. Apart from an increase in height above that expected for the family, 47XYY is not associated with any physical features. • Multifactorial • 1. The chance of having another child with a neural tube defect is 1 in 200. • False • The empiric (observed) probability of having a subsequent child with a neural tube defect is about 1 in 20 when periconceptual vitamin supplementation has not been taken. • 2. The environmental component of the majority of multifactorial conditions has been identified. • False • The environmental component for relatively few multifactorial conditions has been identified - for instance in the neural tube defects. • Mitochondrial • 1. The children of a man with a condition caused by a mutation in mitochondrial DNA will not inherit the condition from him. • True • Mitochondria are inherited from one’s mother and not from one’s father.