1. Human Genetic Disorder
By:-Arnold Jeyan Arulnesan

2. Contents What is Genetic science -3 What is Genetic Disorder -4
Main types of Genetic disorder
Chromosomal disorders
Aneuploidy
Types of aneuploidy
Diseases of aneuploidy
Down Syndrome
Types of DS
Treatment for DS -14
Turner Syndrome
Genetic science
Behind TS
Treatment for TS
Klinefelter syndrome
Deletion
16p11.2 deletion syndrome-26
Other diseases
Inversion
Translocation and diseases -32
Single Gene Disorders
Achondroplasia
Marfan syndrome
Cystic fibrosis
Sickle cell disease
X-linked. The disorder
Other major Genetic Disorder Reasons-43

3. What is Human Genetic science
What is Human Genetic science? (Ref:- Human Genetic Diseases by Dijana Plaseska Karanfilska)
The genetic science is almost 150 years old, and it has astonishing accomplishments during these years. Genetics has become an indispensable component of almost all research in modern biology and medicine. Human genetic variation is a main reason for many human disabilities and disorders. Nowadays “Genetic approach” is being use to gain understanding of many process in human body. Genetic science is investigating any biological process, from the molecular level.
Nowadays we uses genetic science to understand about genetic disorders, How to diagnose them and find out ways to treat them.

4. What is a Human Genetic Disorder? (Ref:- Geneticalliance.org)
A genetic disorder is the result of mutation or changes in an individual DNA. A mutation is a change in the DNA sequence (Sometimes referred to as spelling mistake).
Gene code is vital in production of protein and it carry out most of the work and life function in human body and gene make up most of the cellular structures as well. When gene got mutated protein production will get affected and it can no longer carry out its normal functions. It will result genetic disorder.
Genetic disorder will more often happen in Germ cells, which are the biological cell that gives rise to the gametes. In other words these cells plays vital role in passing genetic information from parents to offspring. So genetic disorders can pass through generations(Inherited). Some Genetic disorders may occur in somatic cells as well or cells in the body which or not germ cells.
Some genetic disorders are rare diseases called as Mendelian disorders which caused by mutation in a single gene DNA sequence. Ex- Huntington’s disease and cystic fibrosis. But large number of disorders are multifactorial which means mutation in several genes.

5. Main Types of Genetic Disorders (Ref:- research paper)
The following are the different types of genetic disorders
Chromosomal abnormalities
Single gene defects
Multifactorial problems
Teratogenic problems

6. What are chromosomal abnormalities?
Chromosomal abnormalities may be inherited from the parent or may occur with no family history as well.
But to understand about this disorder we need know the basics of chromosomes
Every cell in the human body, apart from RBC and the haploid gametes, has 23 pairs of chromosomes (for a total of 46).
One of each pair is inherited from the mother and the other part is inherited from the father. The first 22 pairs of chromosomes are autosomes. The 23rd pair of chromosomes are the sex chromosomes. Normal females have two X chromosomes, while normal males have one X chromosome and one Y chromosome. (Ref:- .

7. Aneuploidy Now we can look in to the common Chromosomal Abnormalities
An increase or decrease of only one or many of the chromosomes in any group of similar chromosomes is called Aneuploidy.
In this condition the number of chromosomes in the nucleus of a cell is not an exact multiple of the Monoploid number of a particular species. An extra or missing chromosome is the main reason for the human genetic disorder. Chromosome abnormalities occur in 1 of 160 live human births
(ref :-
Figure 001
During meiosis when germ cells divide to create sperm and egg (gametes), each half should have the same number of chromosomes. But sometimes, the whole pair of chromosomes will end up in one gamete, and the other gamete will not get chromosome at all. Most embryos cannot survive with a missing or extra Chromosome

8. Type of Aneuploidy (Ref:- www.transtutors.com)
Figure 002
In the somatic cells of aneuploidic organisms if the diploid number of chromosomes are less by one or two chromosomes, the condition is Called as Hypoploidy
Monosomy is the condition in which organisms with Hypoploidy lack only one chromosome of a homologous pair (2n-1). Nullisomy is the condition in which organisms with Hypoploidy lack two chromosomes of a homologous pair
In the somatic cells of aneuploidic organisms if the diploid number of chromosomes is more by one or two it is known as Hyperploidy.
Trisomy is the condition in which Hyperploid organisms have an extra chromosome (2n+1)in any one of the homologous pair of any group of chromosomes.
Polysomy is the condition in which Hyperploid organisms have an increase of more than one chromosomes in a pair.

9. Diseases of Aneuploidy abnormality
Down Syndrome
(Ref: Research paper)
In every cell in the human body there is a nucleus, where genetic material is stored in genes. Genes carry the codes responsible for all of our inherited in chromosomes. Usually nucleus will contain 23 pair of chromosomes. Half of that inherited from parent cell.
Down syndrome will occur when there are only 21 pair of chromosomes fully or partially.
This genetic abnormality will affect human’s character and A few of the common physical problems are
low muscle tone
small stature
upward slant to the eyes
single deep crease across the center of the palm, although different individual with down syndrome may posses different degree of these Characterises

10. There are three types of Down syndrome: trisomy 21 (nondisjunction),
One in every 691 babies in the United States is born with Down syndrome Down syndrome is one of the most common genetic
disorder.
Approximately 400,000 Americans have Down syndrome and about 6,000 babies with Down syndrome are born in the United States each year.
Figure 003
Figure 004
There are three types of Down syndrome:
trisomy 21 (nondisjunction),
translocation
mosaicism

11. Trisomy 21 is the 95% of the cases Down syndrome is usually caused by an error in cell division called "nondisjunction“.
figure 005
2. Mosaicism occurs when nondisjunction of chromosome 21 takes place in one of the initial cell divisions after fertilization. When this occurs, there is a mixture of two types of cells, some containing the usual 46 chromosomes and others containing Those cells with 47 chromosomes contain an extra chromosome 21
Figure 006

12. Causes of Down syndrome ( Ref:- Research paper)
3. Translocation accounts for about 4% of all cases of Down syndrome. In translocation, part of chromosome 21 breaks off during cell division and attaches to another chromosome, typically chromosome 14. While the total number of chromosomes in the cells remain 46, the presence of an extra part of chromosome 21 causes the characteristics of Down syndrome.
Causes of Down syndrome ( Ref: Research paper)
Regardless of the type of Down syndrome all people with Down syndrome have an extra, critical portion of chromosome 21 present in all or some of their cells. This additional Chromosome/s Causes characteristics related to Down syndrome. The cause is still unknown for DS but researches shows that it is increasing with women's ages.
There is no definitive scientific research that indicates that Down syndrome is caused by environmental factors or the parents' activities before or during pregnancy. The additional chromosomes can be originate from father or mother as well, but researches shows traces of 5% of father’s chromosome.

13. Once a woman has given birth to a baby with trisomy 21 (nondisjunction) or translocation, it is estimated that her chances of having another baby with trisomy 21 is 1 in 100 up until age 40.
The risk of recurrence of translocation is about 3% if the father is the carrier and 10-15% if the mother is the carrier. Genetic counselling can determine the origin of translocation.
All 3 types of Down syndrome are genetic disorders, but there is a myth about genetic disorder should run through families but in this case only 1% of cases have a hereditary component, but there is another factor compares Maternal age vs number of DS babies. (fig 007)
Figure 007

14. Treatment for Down Syndrome
(Ref:- Human Genome by :- Patrick James and National Human Genome Research Institute research paper)
Treatment for Down syndrome is based on the person's physical intellectual problems. Many babies who have Down syndrome don’t have good muscle tone, which makes it harder for them to roll over and walk. Physical therapy can help with these problems.
About percent of babies born with Down syndrome have a heart defect. Therefore, all new born with Down syndrome have their heart checked with an electrocardiogram and an echocardiogram.
When there is a heart defect present in an infant with Down syndrome, the infant is referred to a pediatric cardiologist for medical management or to a pediatric cardiac surgeon for early surgical repair.
Some infants with Down syndrome have difficulties with swallowing or they may have blockages in their bowels. Surgery can be performed to correct these problems. Once corrected, they usually cause no further health issues.

15. Children with Down syndrome may have frequent colds and sinus and ear infections. These are treated early and aggressively to prevent hearing loss and chronic infections.
Low thyroid levels are more common in infants who have Down syndrome. It is recommended that thyroid level testing be performed at least yearly.
Some infants with Down syndrome have eye problems such as cataracts or crossed eyes Surgery can help with these problems.
Sucking problems related to low muscle tone or heart problems may make breast feeding difficult initially. Occupational therapists, speech therapists, breast feeding consultants and support groups usually have specific resources for the mothers of infants with Down syndrome.
A research by NIH is clearly saying that Many adults with Down syndrome have jobs and live independently.

16. Turner syndrome (Ref:- Genetics Home Reference)
Another condition by Aneuploidy abnormality is turner syndrome. Turner syndrome is a chromosomal condition that affects development in females (fig 008).
Turner syndrome basic symptom is short stature, which becomes very evident about 5. An early loss of ovarian function is also very common.
figure 008

17. A low hairline at the back of the neck
The ovaries develop normally at first, but egg cells usually die prematurely and most ovarian tissue degenerates before birth. Many affected girls do not undergo puberty unless they receive hormone therapy, and most are unable to conceive
About 30 percent of females with Turner syndrome have extra folds of skin on the neck that called as a webbed neck
other symptoms are
A low hairline at the back of the neck
puffiness or swelling of the hands and feet
skeletal abnormalities and kidney problems
one half of individuals with Turner syndrome are born with a heart defect. Mainly narrowing of the large artery leaving the heart or in other terms (fig 009) abnormalities of the valve that connects the aorta with the heart.
These heart defects
Can be life-threatening.
Figure 009

18. Developmental delays, nonverbal learning disabilities, and behavioural problem are the other symptoms occur in boys and girls affected by Turner syndrome but the degree of the characteristics may defer from one to another.
This condition occurs in about 1 in 2,500 new born girls worldwide.
Genetic Science Behind Turner syndrome
Turner syndrome is related to the X chromosome which is one of the two sex chromosomes.
People typically have two sex chromosomes in each cell Male XY Female XX.
Turner syndrome results when one normal X chromosome is present in a female's cells and the other sex chromosome is missing or structurally destroyed
The missing genetic material is the reason for these condition and that is the main reason for variable characteristics as well.
About half of individuals with Turner syndrome have only one X chromosome, which means each cells in the body has only one copy of X chromosomes. Instead of two.

19. Turner syndrome can also occur if one of the sex chromosomes is partially missing or rearranged rather than completely absent.
A person having turner syndrome have chromosomal change in some cells only. This condition called as ‘Mosaicism’, so its called mosaic turner syndrome.
Researchers have not identified which genes on the X chromosome are more associated with Turner syndrome.
They have, however identified one gene called SHOX that is important for bone development and growth. The loss of one copy of this gene likely causes short stature and skeletal abnormalities in women with Turner syndrome.
Turner syndrome is a chromosomal disorder, but they are not inherited.
chromosomal abnormality occurs as a random event during the formation of reproductive cells such as eggs and sperm.
Rarely, Turner syndrome caused by a partial deletion of the X chromosome can be passed from one generation to the next.

20. Figure 010
According figure 010 when a sperm with a missing copy of Y chromosome combined with a normal egg it called as Retarded infertile and that creates turner syndrome.
Treatment for Turner Syndrome (Ref:- Human Genome By Patrick James and National Human Genome Research Institute research paper)
During childhood and adolescence, girls may be under the care of a pediatric endocrinologist, who is a specialist in childhood conditions of the hormones and metabolism.
Growth hormone injections are beneficial in some individuals with Turner syndrome. Injections often begin in early childhood and may increase final adult height by a few inches.

21. Oestrogen replacement therapy is another solution for this problem
Oestrogen replacement therapy is another solution for this problem. Then slowly Breast development will start.
Oestrogen and progesterone are given a little later to begin a monthly 'period,' which is necessary to keep the womb healthy. Oestrogen is also given to prevent osteoporosis.
Babies born with a heart narrowing of the aorta may need surgery to correct the problem. A heart expert (cardiologist) will assess and follow up any treatment necessary.
Girls who have Turner syndrome are more likely to get middle ear infections. Repeated infections may lead to hearing loss and should be evaluated by the paediatrician.
High blood pressure is quite common in women who have Turner syndrome. In some cases, the elevated blood pressure is due to narrowing of the aorta or a kidney abnormality. Blood pressure should be checked routinely and, if necessary we should take medications.
Women who have Turner syndrome have a slightly higher risk of having an under active thyroid or developing diabetes. This should also be monitored during routine health maintenance visits and treated if necessary.

22. Klinefelter syndrome (Ref:- Medical net John P. Cunha page)
There are many Aneuploidy abnormality related diseases founded with the improvement of genetic science.
Klinefelter syndrome (Ref:- Medical net John P. Cunha page)
Klinefelter syndrome, also known as the XXY condition, is a term used to describe males who have an extra X chromosome in most of their cells.
About one of every 500 males has an extra X chromosome, but many don't have any symptoms.
Symptoms depend on how many XXY cells a man has, how much testosterone is in his body, and his age when the condition is diagnosed.
Figure 013 Explains how this process happens.
Figure 013
Figure 014

23. As XXY males enter puberty, they may have a taller, less muscular body, less facial and body hair, and broader hips than other boys. As teens, XXY males may have larger breasts, weaker bones, and a lower energy level than other boys.
XXY adult males look similar to males without the condition, although they are often taller and may have autoimmune disorders, breast cancer, vein diseases, osteoporosis, and tooth decay.
XXY males can have normal sex lives, but they usually make little or no sperm and are infertile.
The XXY chromosome pattern cannot be changed. Treatments involve physical, speech, occupational, behavioural, mental health, and family therapists, and testosterone replacement therapy (TRT).
Likewise there are many diseases in Aneuploidy abnormality
polysomy X and/or Y – Abnormal male
tetrasomy X, pentasomy X – Abnormal Female

24. Next type of Chromosomal Abnormality is Deletion. What is DELETION
Figure 011
Part of a chromosome is missing, or part of the DNA code is missing. This of course involves loss of genetic information and results in what could be considered "partial monosomy" for that chromosome. This is a structural abnormality

25. Structural rearrangements frequently alter chromosome
morphology. Chromosome morphology is based upon
location of the centromere or primary constriction that
divides a chromosome into a short arm ‘p’ and a long arm q.
Figure 012
According the figure 012 The small d gene part is deleted from one chromosome and got inserted in the other this is called as Deletion.
Chromosomes are metacentric when the centromere is in the middle with short and long arms of roughly equal length
submetacentric when the centromere is closer to one end with short and long arms of unequal length

26. Acrocentric when the centromere is near one end with very small short arms. The centromere is essential for correct segregation of chromosomes during cell division. DNA replication prior to cell division ensures that each chromosome consists of two identical sister chromatids joined at the centromere.
The major Diseases of Deletion is 16p11.2 deletion syndrome. (Ref:- U.S. National Library of Medicine)
16p11.2 deletion syndrome is a disorder caused by a deletion of a small piece of chromosome 16. The deletion occurs near the middle of the chromosome at a location designated p11.2.
People with 16p11.2 deletion syndrome usually have developmental delay and intellectual disability. Most also have at least some features of autism spectrum disorders.
these disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language
Figure013

27. Some affected individuals have minor physical abnormalities such as low set ears or partially webbed toes.
People with this disorder are also at increased risk of obesity compared with the general population. However, there is no particular pattern of physical abnormalities that characterizes 16p11.2 deletion syndrome.
Signs and symptoms of the disorder vary even among affected members of the same family. Some people with the deletion have no identified physical, intellectual, or behavioural abnormalities.
In the general population it has been estimated at approximately 3 in 10,000 having this disorder.
There are lots of complicated steps take place in this disorder deletion syndrome are missing a sequence of about 600,000 DNA building blocks (base pairs),but make it simple the whole process is shown in fig 014, so the breakage can happen in either side of centriole
Figure 014

28. There are many other examples for deletion disorder such as.
Wolf–Hirschhorn syndrome
also known as chromosome deletion Dillan 4p syndrome. Wolf–Hirschhorn syndrome is caused by a partial deletion of the short arm of chromosome 4.
About 87% of cases represent a de novo deletion, while about 13% are inherited from a parent with a chromosome translocation.
Williams Syndrome
This is a rare neurodevelopmental disorder. It is caused by a deletion of about 26 genes from the long arm of chromosome 7. It occurs in 1 in 7,500 to 1 in 20,000 births.
The most common symptoms of Williams syndrome are heart defects, and unusual facial features. Other symptoms include failure to gain weight appropriately in infancy and low muscle tone.
Most individuals with Williams syndrome are highly verbal relative to their IQ, and are overly sociable, having what has been described as a "cocktail party" type personality. It is in some respect the opposite of autism (Ref:- genome.gov)

29. Alfi's Syndrome
This is a rare chromosomal disorder in which there is deletion (monosomy) of a portion of chromosome 9. Symptoms include microgenitalia, mental retardation with microcephaly and dysmorphic features.
Kleefstra syndrome
Terminal deletions of chromosome 9q34 have been associated with childhood hypotonia (Hypotonia is a state of low muscle tone). A distinctive facial appearance and developmental disability. The facial features typically described include arched eyebrows, small head circumference, midface hypoplasia, prominent jaw and a pouting lower lip. Individuals with this disease may often have speech impediments, such as speech delays.
Jacobsen syndrome
This is a rare congenital disorder(is a condition existing at birth and often before birth, structural deformities) resulting from deletion of a terminal region of chromosome 11 that includes band 11q24.1. It can cause intellectual disabilities, a distinctive facial appearance, and a variety of physical problems including heart defects and a bleeding disorder

30. The next type of chromosomal disorder is Inversion
Inversion (Medical net and NIH research paper)
When a chromosome breaks and the piece of the chromosome turns upside down and reattaches itself. Inversions may or may not cause birth defects depending on their exact structure.
Please Refer fig 015
A chromosome inversion can be inherited from one or both parents, or it may be a mutation that appears in a child whose family has no history of chromosome inversion.
There are two types of inversion
Balanced and un balanced
An inversion can be 'balanced,' meaning that it has all the genes that are present in a normal chromosome; or it can be 'unbalanced,' meaning that genes have been deleted (lost) or duplicated
Figure 015

31. A balanced inversion causes no problems
A balanced inversion causes no problems. An unbalanced inversion is often associated with problems such as developmental delay, mental retardation, and birth defects.
An inversion does not involve a loss of genetic information, but simply rearranges the linear gene sequence.
Families that may be carriers of inversions may be offered genetic counselling and genetic testing.
Cytogenetic techniques may be able to detect inversions, or inversions may be inferred from genetic analysis. Nevertheless, in most species small inversions go undetected. In insects with polytene chromosomes, for example Drosophila(is a genus of small flies), preparations of larval salivary gland chromosomes allow inversions to be seen when they are heterozygous(A diploid organism is heterozygous).

32. The next type of chromosomal disorder is Translocation (Ref:- Rochester medical centre research document)
Translocation. A rearrangement of a chromosome segment from one location to another, either within the same chromosome or to another.
Reciprocal translocation. The DNA is equally exchanged between chromosomes, and none is lost or added. A parent with a balanced translocation is healthy, but he or she may be at risk for passing unbalanced chromosomes in a pregnancy.
Robertsonian translocation A balanced translocation in which one chromosome joins the end of another.
Figure 016

33. Will translocation can inherit through generations?
This is a question that need to be answered to get the correct treatment for this condition.
Answer:- Not Always. There are possibilities for this to happen
The child may inherit entirely normal chromosomes.
The child may inherit the same balanced translocation as the parent. In most cases the child will not have any problems as a result of the translocation.
The child may inherit an unbalanced translocation, and may be born with some degree of developmental delay, learning disability and health problems.
Tests for chromosome translocations
Genetic testing is available to find out whether a person carries a translocation. A simple blood test is done, and cells from the blood are examined in a laboratory to look at the arrangement of the chromosomes. This is called a karyotype test. It is also possible to do a test during pregnancy to find out whether a baby has a chromosome translocation. This is called prenatal diagnosis and is something you may wish to discuss with the genetic specialist.

34. The disorders from translocation of chromosomes.
Burkitt's lymphoma (Ref:- Human resource and development management research paper)
is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal centre.
Three types are there
The endemic variant
more occur in children living in malaria endemic regions.
The sporadic type
is the most common variant found in places where malaria is not holoendemic(A disease is holoendemic when essentially every individual in a population is infected)
3. Immunodeficiency-associated Burkitt lymphoma
More occur in HIV cases.

35. Single gene disorders
These are also known as Mendelian inheritance disorders, from the first genetic work of Gregor Mendel. In these disorders, a single gene is responsible for a defect or abnormality. Single gene disorders usually have greater risks of inheritance. Single gene disorders can be:
Dominant. An abnormality occurs when only one of the genes from one parent is abnormal. If the parent has the disorder, the baby has a 50 percent chance of inheriting it. Examples include the following:
Achondroplasia.
The skeletal dysplasia's are a heterogeneous group of disorders characterized by intrinsic abnormalities in the growth and remodeling of cartilage and bone.
These dysplasias affect the skull, spine, and extremities in varying degrees. They frequently cause a disproportionately short stature .

36. Figure017
The standing height falls below the third percentile for age. Achondroplasia is the most common type of short-limb disproportionate dwarfism. The term achondroplasia, implying absent cartilage formation.

37. Marfan syndrome this is another dominant condition(Ref:- Emedcine Medscape)
Marfan syndrome (MFS) is a spectrum disorder caused by a heritable genetic defect of connective tissue that has an autosomal dominant mode of transmission.
The defect itself has been isolated to the FBN1 gene on chromosome 15, which codes for the connective tissue protein fibrillin.
Abnormalities in this protein cause a myriad of distinct clinical problems, of which the musculoskeletal, cardiac, and ocular system problems predominate.
The skeleton of patients with MFS typically displays multiple deformities including arachnodactyly (abnormally long and thin digits), dolichostenomelia (long limbs relative to trunk length), pectus deformities ( pectus excavatum and pectus carinatum)and thoracolumbar scoliosis.

38. . Recessive
An abnormality only occurs when both parents have abnormal genes. If both parents are carriers, a baby has a 25 percent chance of having the disorder. Examples include the following
Cystic fibrosis
Cystic fibrosis is an inherited disease characterized by the build-up of thick, sticky mucus that can damage many of the body's organs.
The disorder's most common signs and symptoms include progressive damage to the respiratory system and chronic digestive system problems. The features of the disorder and their severity varies among affected individuals.
Mucus is a slippery substance that lubricates and protects the linings of the airways, digestive system, reproductive system, and other organs and tissues.
In people with cystic fibrosis, the body produces mucus that is abnormally thick and sticky. This abnormal mucus can clog the airways, leading to severe problems with breathing and bacterial infections in the lungs. These infections cause chronic coughing, wheezing, and inflammation. Over time, mucus buildup and infections result in permanent lung damage, including the formation of scar tissue (fibrosis) and cysts in the lungs.

39. Most people with cystic fibrosis also have digestive problems
Most people with cystic fibrosis also have digestive problems. Some affected babies have meconium ileus, a blockage of the intestine that occurs shortly after birth.
In people with cystic fibrosis, mucus blocks the ducts of the pancreas, reducing the production of insulin and preventing digestive enzymes from reaching the intestines to aid digestion. Problems with digestion can lead to diarrhoea, malnutrition, poor growth, and weight loss.
In adolescence or adulthood, a shortage of insulin can cause a form of diabetes known as cystic fibrosis-related diabetes mellitus
Mutations in the CFTR gene cause cystic fibrosis. The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells.
Chloride is a component of sodium chloride, a common salt found in sweat. Chloride also has important functions in cells for example, the flow of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus.

40. Sickle cell disease. (Ref:-U.S. National Library of medicine)
Mutations in the CFTR gene disrupt the function of the chloride channels, preventing them from regulating the flow of chloride ions and water across cell membranes. As a result, cells that line the passageways of the lungs, pancreas, and other organs produce mucus that is unusually thick and sticky
Figure 018
Sickle cell disease. (Ref:-U.S. National Library of medicine)
Sickle cell disease is a group of disorders that affects haemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body.
People with this disorder have atypical haemoglobin molecules called haemoglobin S, which can distort red blood cells into a sickle, or crescent, shape.
Signs and symptoms of sickle cell disease usually begin in early childhood. Characteristic features of this disorder include a low number of red blood cells (anaemia), repeated infections, and periodic episodes of pain.

41. The signs and symptoms of sickle cell disease are caused by the sickling of red blood cells. When red blood cells sickle, they break down prematurely, which can lead to anaemia.
Anaemia can cause shortness of breath, fatigue, and delayed growth and development in children. The rapid breakdown of red blood cells may also cause yellowing of the eyes and skin, which are signs of jaundice. Painful episodes can occur when sickled red blood cells, which are stiff and inflexible, get stuck in small blood vessels.
These episodes deprive tissues and organs of oxygen-rich blood and can lead to organ damage, especially in the lungs, kidneys, spleen, and brain.
A particularly serious complication of sickle cell disease is high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Pulmonary hypertension occurs in about one-third of adults with sickle cell disease and can lead to heart failure.
Mutations in the HBB gene cause sickle cell disease
Hemoglobin consists of four protein subunits, typically, two subunits called alpha-globin and two subunits called beta-globin. The HBB gene provides instructions for making beta-globin. Various versions of beta-globin result from different mutations in the HBB gene. One particular HBB gene mutation produces an abnormal version of beta-globin known as hemoglobin S (HbS).

42. Duchenne muscular dystrophy.
X-linked. The disorder
Is determined by genes on the X chromosome. Males are mainly affected and have the disorder. Daughters of men with the disorder are carriers of the trait and have a one in two chance of passing it to their children. Sons of women who are carriers each have a one in two chance of having the disorder. Examples include the following:
Duchenne muscular dystrophy.
A disease of muscle wasting.
Haemophilia.
Hemophilia is a bleeding disorder that slows the blood clotting process. People with this condition experience prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled. In severe cases of hemophilia, continuous bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding).

43. multifactorial problems
Other than chromosomal disorder and single gene disorder there some other reasons for genetic disorder as well
multifactorial problems
Some birth defects do not follow a single gene or chromosomal abnormality pattern. They may be due to several problems, or a combined effect of genes and the environment. It is difficult to predict inheritance of abnormalities caused by multiple factors. Examples include heart defects, cleft lip or cleft palate, and neural tube defects (defects in the spine or brain).

44. teratogenic problems
Certain substances are known to cause abnormalities in babies. Many birth defects occur when the fetus is exposed to teratogens (substances that cause abnormalities) during the first trimester of pregnancy when organs are forming. Some known teratogens include the following:
Certain medications (always consult your doctor before taking any medications during pregnancy)
Alcohol
High level of radiation exposure
Lead
Certain infections (such as rubella)