If a woman has three male offspring what is the probability that her next child will be female

When a genetic disorder is diagnosed in a family, family members often want to know the likelihood that they or their children will develop the condition. This can be difficult to predict in some cases because many factors influence a person's chances of developing a genetic condition. One important factor is how the condition is inherited. For example:

• Autosomal dominant inheritance: A person affected by an autosomal dominant disorder

  
  has a 50 percent chance of passing the altered gene to each child. The chance that a child will not inherit the altered gene is also 50 percent. However, in some cases an autosomal dominant disorder results from a new (de novo) variant
  
  that occurs during the formation of egg or sperm cells or early in embryonic development. In these cases, the child's parents are unaffected, but the child may pass on the condition to his or her own children.

• Autosomal recessive inheritance: Two unaffected people who each carry one copy of the altered gene for an autosomal recessive disorder

  
  (carriers) have a 25 percent chance with each pregnancy of having a child affected by the disorder. The chance with each pregnancy of having an unaffected child who is a carrier of the disorder is 50 percent, and the chance that a child will not have the disorder and will not be a carrier is 25 percent. If only one parent is a carrier of the altered gene and the other parent does not carry the variant, none of their children will develop the condition, and the chance with each pregnancy of having an unaffected child who is a carrier is 50 percent. 

• X-linked dominant inheritance: The chance of passing on an X-linked dominant condition

  
  differs between men and women because men have one X chromosome and one Y chromosome, while women have two X chromosomes. A man passes on his Y chromosome to all of his sons and his X chromosome to all of his daughters. Therefore, the sons of a man with an X-linked dominant disorder will not be affected, but all of his daughters will inherit the condition. A woman passes on one or the other of her X chromosomes to each child. Therefore, a woman with an X-linked dominant disorder has a 50 percent chance of having an affected daughter or son with each pregnancy.

• X-linked recessive inheritance: Because of the difference in sex chromosomes, the probability of passing on an X-linked recessive disorder

  
  also differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the altered gene. With each pregnancy, a woman who carries an altered gene for X-linked recessive has a 50 percent chance of having sons who are affected and a 50 percent chance of having daughters who carry one copy of the altered gene. Females with one gene variant associated with an X-linked recessive disorder typically have no or very mild signs or symptoms of the condition.

• X-linked: Because the inheritance pattern of many X-linked disorders is not clearly dominant or recessive, some experts suggest that conditions be considered X-linked rather than X-linked dominant or X-linked recessive. As above, the probability of passing on an X-linked disorder differs between men and women. The sons of a man with an X-linked disorder will not be affected, but all of his daughters will inherit the altered gene and may develop signs and symptoms of the condition. A woman passes on one or the other of her X chromosomes to each child. Therefore, with each pregnancy, a woman with an X-linked disorder has a 50 percent chance of having a child with the altered gene. An affected daughter may have milder signs and symptoms than an affected son. 

• Y-linked inheritance: Because only males have a Y chromosome, only males can be affected by and pass on Y-linked disorders

  
  . All sons of a man with a Y-linked disorder will inherit the condition from their father.

• Codominant inheritance: In codominant inheritance

  
  , each parent contributes a different version of a particular gene, and both versions influence the resulting genetic trait. The chance of developing a genetic condition with codominant inheritance, and the characteristic features of that condition, depend on which versions of the gene are passed from parents to their child.

• Mitochondrial inheritance: Mitochondria, which are the energy-producing centers inside cells, each contain a small amount of DNA. Disorders with mitochondrial inheritance

  
  result from variants in mitochondrial DNA. Although these disorders can affect both males and females, only females can pass variants in mitochondrial DNA to their children. A woman with a disorder caused by changes in mitochondrial DNA will pass the variants to all of her daughters and sons, but the children of a man with such a disorder will not inherit the variant.

It is important to note that the chance of passing on a genetic condition applies equally to each pregnancy. For example, if a couple has a child with an autosomal recessive disorder, the chance of having another child with the disorder is still 25 percent (or 1 in 4). Having one child with a disorder does not “protect” future children from inheriting the condition. Conversely, having a child without the condition does not mean that future children will definitely be affected.

Although the chances of inheriting a genetic condition appear straightforward, factors such as a person's family history and the results of genetic testing can sometimes modify those chances. In addition, some people with a disease-causing variant never develop any health problems or may experience only mild symptoms of the disorder. If a disease that runs in a family does not have a clear-cut inheritance pattern, predicting the likelihood that a person will develop the condition can be particularly difficult.

Estimating the chance of developing or passing on a genetic disorder can be complex. Genetics professionals can help people understand these chances and help them make informed decisions about their health.