Human Genetics: Matters of Sex - PDF

Because learning changes everything.® Chapter 06 Matters of Sex HUMAN GENETICS Concepts and Applications Fourteenth Edition Ricki Lewis © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  Learning Out...

Because learning changes everything.® Chapter 06 Matters of Sex HUMAN GENETICS Concepts and Applications Fourteenth Edition Ricki Lewis © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  Learning Outcomes 1 1. Describe the factors that contribute to whether we are and feel male or female. 2. Distinguish between the X and Y chromosomes. 3. Discuss how manipulating the sex ratio can affect societies. 4. Distinguish between Y linkage and X linkage. 5. Compare and contrast X-linked recessive inheritance and X-linked dominant inheritance. 6. Discuss the inheritance pattern of a trait that appears in only one sex. 7. Define sex-influenced trait. © McGraw Hill 2  Learning Outcomes 2. Explain why X inactivation is necessary.. Explain how X inactivation is an epigenetic change.. Discuss how X inactivation affects the phenotype in female mammals.. Loading… Explain the chemical basis of silencing the genetic contribution from one parent.. Explain how differences in the timetables of sperm and oocyte formation can lead to parent-of-origin effects. © McGraw Hill 3  Our Sexual Selves Biological maleness or femaleness is determined at conception Biological female inherits two X chromosomes or biological male inherits an X and a Y Another level of sexual identity comes from the control that hormones exert on development of reproductive structures. Biological factors and social cues influence sexual feelings. Gender identity © McGraw Hill 4  The Male Reproductive System 2 Loading… Biophoto Associates/ Photo Researchers/Science Source Access the text alternative for slide images. © McGraw Hill 5  Sexual Development 1 During the fifth week of prenatal development, all embryos develop two sets of: Unspecialized gonads Reproductive ducts—Müllerian (female-specific) and Wolffian (male-specific) An embryo develops as a male or female based on the sex chromosome constitution and actions of certain genes SRY gene (sex-determining region of the Y chromosome) Wnt4 gene (essential for development and maturation as a biological female) © McGraw Hill 6  Sexual Development 2 Femaleness once considered “default” option in human development ─ absence of maleness Sex determination more accurately described as fate imposed on ambiguous precursor structures Mutations in Wnt4 cause: X X female to develop high levels male sex hormones A lack of development of vaginal canal and uterus Ovaries that do not develop properly © McGraw Hill 7  The Organs of Reproduction Access the text alternative for slide images. © McGraw Hill 8  Sex Chromosomes 1 Human males are the heterogametic sex with different sex chromosomes (X Y). Human females are the homogametic sex (X X). In other species sex can be determined in many ways. For example, in birds and snakes, males are homogametic (Z Z), while females are heterogametic (Z W). © McGraw Hill 9  Sex Chromosomes 2 X chromosome Contains > 1500 genes Much larger than the Y chromosome Acts as a homolog to Y in males Y chromosome Contains 231 genes Does not cross over along all of its length Many DNA segments are palindromes and may destabilize DNA replication © McGraw Hill 10  Anatomy of the Y Chromosome 1 The Y chromosome has a very short arm and a long arm Pseudoautosomal regions (P A R 1 and P A R 2) 5% of the chromosome Contain 63 genes shared with X chromosome Loading… Control bone growth, cell division, etc. in both sexes Male specific region (M S Y) Most of the chromosome Three classes of DNA sequences Sequence almost identical to the X chromosome, somewhat identical to the X chromosome, palindromes Many of the genes are essential to fertility Including SRY © McGraw Hill 11  Anatomy of the Y Chromosome 2 Access the text alternative for slide images. © McGraw Hill 12  SRY Gene Encodes a transcription factor protein Controls the expression of other genes, including Sox9 Stimulates male development Sends signals to the indifferent gonads to destroy female structures Stimulates development of male structures Testosterone and dihydrotestosterone (DHT) are secreted Stimulate development of male reproductive structures © McGraw Hill 13  Disorders of Sex Development 1 Hermaphroditism is an older and more general term for an individual with male and female sexual structures. Intersex refers to individuals whose internal structures are inconsistent with external structures, or whose genitalia are ambiguous. Pseudohermaphroditism refers to the presence of both female and male structures but at different life stages. © McGraw Hill 14  Disorders of Sex Development 2 Pseudohermaphroditism includes: Androgen insensitivity syndrome Mutation on the X-chromosome blocks formation of androgen receptors 5-alpha reductase deficiency Unable to convert testosterone to DHT Child has inside male anatomy but looks like a girl on the exterior Congenital adrenal hyperplasia Enzyme block causes androgens to accumulate Cause precocious puberty in males or male secondary sex characteristics to develop in females. © McGraw Hill 15  Mutations That Affect Male Sexual Development Access the text alternative for slide images. © McGraw Hill 16  Same-Sex Attraction 1 Person’s phenotype and genotype are consistent Physical attraction is toward members of the same sex Same-sex attraction has been seen in all cultures for thousands of years Documented in over 1500 animal species © McGraw Hill 17  Same-Sex Attraction 2 Evidence suggests a complex input from both genes and the environment. Identical twins are more likely to be attracted to the same sex than members of fraternal twin pairs. Genetic markers were identified on the X chromosome more often identical among pairs of same-sex attracted brothers. One study has concluded that “many tiny genetic effects” may contribute to same-sex attraction. So, there is no one specific gene that determines attraction to the same or opposite sex. © McGraw Hill 18  Components of Sexual Identity Table 6.1 Sexual Identity Level Events Timing Chromosomal/ XY = male Fertilization genetic sex XX = female Gonadal sex Undifferentiated structure begins to 6 weeks after develop as testis or ovary fertilization Phenotypic sex Development of external and internal 8 weeks after reproductive structures continues as fertilization, at male or female in response to puberty hormones Gender identity Strong feelings of being male, female, From childhood, or nonbinary develop possibly earlier Sexual orientation Attraction to same or opposite sex From childhood © McGraw Hill 19  Sex Ratios The proportion of males to females in a human population Calculated by # of males/# of females multiplied by 1000 Primary sex ratio—At conception Secondary sex ratio—At birth Tertiary sex ratio—At maturity Sex ratios can change markedly with age Reflects medical conditions and environment factors © McGraw Hill 20  Y-Linked Traits Genes on the Y chromosome are said to be Y-linked Y-linked traits are very rare Transmitted from male to male A female does not have a Y chromosome Currently, identified Y-linked traits involve infertility and are not transmitted © McGraw Hill 21  X-Linked Traits Patterns of expression on the X chromosome differ in females and males. Females—X-linked traits are passed like autosomal traits. Males—A single copy of an X-linked allele causes expression of the trait or illness. Human male is considered hemizygous for X-linked traits. © McGraw Hill 22  Sex Determination in Humans Access the text alternative for slide images. © McGraw Hill 23  Introducing Cells Table 6.2 Comparison of X-Linked Recessive and X-Linked Dominant Inheritance X-Linked Recessive Trait X-Linked Dominant Trait Always expressed in the male Expressed in females in one copy Expressed in a female homozygote Much more severe effects in males and very rarely in a female heterozygote Affected male inherits trait from High rates of miscarriage due to heterozygote or homozygote early lethality in males mother Affected female inherits trait from Passed from male to all daughters affected father and affected or but to no sons heterozygote mother © McGraw Hill 24  X-Linked Recessive Traits 1 An X-linked recessive trait is expressed in females if the causative allele is present in two copies. If condition is not lethal, a man may be healthy enough to transmit it to offspring Examples: Ichthyosis = Enzyme deficiency blocks removal of cholesterol from skin cells Colorblindness = About 8% of males of European ancestry have the condition Hemophilia = Disorder of blood-clotting © McGraw Hill 25  X-Linked Recessive Traits 2 Ichthyosis Courtesy, Dr. Mark A. Crowe Access the text alternative for slide images. © McGraw Hill 26  X-Linked Recessive Traits 3 Hemophilia B Access the text alternative for slide images. © McGraw Hill 27  X-Linked Dominant Traits 1 Dominant X-linked traits are rare. Gene expression differs between the sexes A female who inherits a dominant X-linked allele or in whom the mutation originates has the associated trait But a male who inherits the allele is usually more severely affected because he has no other allele to mask its effect. Most cases are the result of new mutations, rather than transmission from a parent Examples: Rett syndrome (Refer to Chapter 2 opener) Incontinentia pigmenti © McGraw Hill 28  X-Linked Dominant Traits 2 Incontinentia pigmenti Loading… Access the text alternative for slide images. © McGraw Hill 29  X-Linked Dominant Traits 3 Courtesy, Richard Alan Lewis M.D., M.S., Baylor College of Medicine © McGraw Hill 30  Solving Genetic Problems Steps to follow: 1. Look at the inheritance pattern. 2. Draw a pedigree. 3. List genotypes and phenotypes and their probabilities. 4. Assign genotypes and phenotypes to parents. 5. Determine how alleles separate into gametes. 6. Unite the gametes in a Punnett square. 7. Determine the phenotypic and genotypic ratios for theF1 generation. 1. To predict further generations, use the genotypes of theF1 and repeat steps 4 to 6. © McGraw Hill 31  Sex-Limited Traits Traits that affect a structure or function that is present in only one sex The gene may be autosomal or X-linked Examples: Beard growth Milk production Preeclampsia in pregnancy A gene from the father may affect the placenta in a way that elevates the pregnant woman’s blood pressure. © McGraw Hill 32  Sex-Influenced Traits Allele is dominant in one sex but recessive in the other The gene may be autosomal or X-linked Difference in expression can be caused by hormonal differences between sexes Examples: Pattern baldness in humans A heterozygous male is bald, but a heterozygous female is not Response to treatment for glioblastoma Female patients live longer than male patients after surgery, radiation, and use of a drug, temozolomide. © McGraw Hill 33  X Inactivation 1 Females have two alleles for X chromosome genes but males have only one. In mammals, X inactivation balances this inequality in the expression of genes on the X chromosome. A female mammal is a mosaic for expression of most genes on the X chromosome. XIST gene encodes an RNA that binds to and inactivates the X chromosome. © McGraw Hill 34  X Inactivation 2 X inactivation occurs early in prenatal development The adult female has patches of tissue that differ in their expression of X-linked genes Alters the phenotype and not the genotype It is an example of an epigenetic change An inherited change that does not alter the DNA base sequence Inactivated DNA has chemical methyl (CH3 ) groups bound to it that prevent it from being transcribed into RNA © McGraw Hill 35  X Inactivation 3 Access the text alternative for slide images. © McGraw Hill 36  Effect of X Inactivation on the Phenotype 1 X inactivation can be used to check the sex of an individual Nucleus of a cell of a female, during interphase, contains a Barr body The consequences of X inactivation on the phenotype can be interesting Homozygous X-linked genotypes—No effect Heterozygotes—Leads to expression of one allele or the other © McGraw Hill 37  Effect of X Inactivation on the Phenotype 2 A female that expresses the phenotype corresponding to an X-linked gene is a manifesting heterozygote. X inactivation is obvious in calico cats. G.K. & Vikki Hart/Getty Images © McGraw Hill 38  Effect of X Inactivation on the Phenotype 3 In humans, X inactivation can be used to identify carriers of some X-linked disorders Hunter syndrome (mucopolysaccharidosis II) Lesch-Nyhan syndrome Affects the severity of Rett syndrome X inactivation plays a role in the severity of COVID 19 Unequal X inactivation pattern can occur if the two X chromosomes have different alleles for a gene that controls cell division Gives certain cells a survival advantage © McGraw Hill 39  Parent-of-Origin Effects In Mendel’s experiments, it didn’t matter whether a trait came from the male or female parent For some genes, parental origin influences phenotype Age of onset of disease Symptom severity Mechanisms of parent-of-origin effects Genomic imprinting Differences between developmental timetables of sperm and oocytes © McGraw Hill 40  Genomic Imprinting 1 In genomic imprinting, methyl (CH3 ) groups bind a gene or several linked genes Prevent them from being expressed For an imprinted gene, the copy inherited from either the father or the mother is always covered with methyls, even in different Designed by Mark Sherman. Provided by Arthur individuals. Riggs and Craig Cooney. © McGraw Hill 41  Genomic Imprinting 2 Parental effect on gene expression is seen as diseases inherited from a parent For example, central precocious puberty is always inherited from the father. A gene called MKRN3 from the father is covered in methyls, and therefore imprinted. In this condition, girls reach puberty before age 8 and boys before age 9. Epigenetic alteration—Layer of meaning stamped upon a gene without changing its DNA sequence © McGraw Hill 42  Genomic Imprinting 3 Imprints are erased during meiosis. Then reassigned based on instituted according to the sex of the individual Access the text alternative for slide images. © McGraw Hill 43  Importance of Genomic Imprinting 1 Function of imprinting isn’t well understood, may be a way to regulate abundance of key proteins in the embryo. Imprinted genes are in clusters along a chromosome, controlled by imprinting centers. One gene in a cluster could be essential for early development. Others become imprinted due to bystander effect. © McGraw Hill 44  Importance of Genomic Imprinting 2 Research suggests that it takes two opposite sex parents to produce a healthy embryo Male genome controls placenta development Female genome controls embryo development Genomic imprinting may also explain incomplete penetrance May be a concern in assisted reproductive technologies © McGraw Hill 45  Imprinting and Human Disease 1 Humans have 150+ imprinted genes, and at least 60 of them affect health if abnormally expressed Two distinct syndromes result from a small deletion in chromosome 15 Prader-Willi syndrome Deletion inherited from father Angelman syndrome Deletion inherited from mother Abnormal imprinting is associated with: Diabetes mellitus; Autism; Alzheimer disease Schizophrenia; male-male attraction © McGraw Hill 46  Imprinting and Human Disease 2 Deletion on chromosome 15 reveals imprinting. (b): Carla D. Kipper (c): Dan James/Caters News Agency Access the text alternative for slide images. © McGraw Hill 47  Different Timetables in Sperm and Oocyte Formation Differences in development of sperm and oocytes explain some parent-of-origin effects. Huntington disease Has younger age of onset, with faster and more severe symptoms, if inherited from the father Noonan syndrome Children of older fathers have an increased risk © McGraw Hill 48  End of Main Content Because learning changes everything.® www.mheducation.com © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.